1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/16111629.csml convertedTime:2009.07.01.10:52

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title TLR ignores methylated RNA?
Authors Ishii KJ, Akira S.
Affiliation ERATO, Japan Science and Technology Agency (JST), Osaka University.
Abstract CpG methylation of DNA silences TLR9-mediated innate immune recognition. In thisissue of Immunity, Kariko et al (2005) suggest that the innate immunerecognition of RNA by TLR3, TLR7, or TLR8 is in fact controlled by modificationof nucleotides, including methylation.
PMID 16111629
Model Abstract

Entity

G010329:TNF-alpha G010657:IL-12 p40 G016992:IFN-alpha1 MO000000058:NF-kappaB MO000000289:TNF-alpha MO000016573:MyD88 MO000016659:IFNalpha1 MO000017264:IL-8 MO000017265:IL-12 MO000019398:TLR3 MO000022224:dsRNA MO000041125:TRIF MO000041446:dsRNA:TLR3 MO000042007:TLR8 MO000042012:TLR9 MO000042126:TLR7 MO000103999:Mda-5 e1: e10: e11: e12:ssRNA e13:ssRNA: TLR7 e14:ssRNA: TLR8 e15:CpG DNA: TLR9 e16:CpG DNA e17:RIG-1 e18:dsRNA: RIG-1 e19:siRNA e2: e20:SiRNA: TLR7 e21:SiRNA: TLR8 e22:dsRNA: Mda-5 e23:MyD88{activated} e24:NF-kappaB{activated} e25:IL-8 e26:synthetic RNA e27:synthatic RNA: TLR7 e28:synthetic RNA: TLR8 e29:synthetic RNA: TLR3 e3: e30:TRIF{activated} e31:N6-methyaladanosine e4: e5: e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6: e60: e61: e62: e7: e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p3 p4 p5 p6 p7 p8 p9
Model Detail
735.0, 785.0
28.5, 28.5

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p14

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
736.0, 830.0
30.0, 30.0

IL-12 p40

--

G010657

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p23

true true true true

csml-variable:Double

m93589

10

false

infinite

0

unit false false false
TRANSFACG010657

--

Go back
754.0, 872.0
30.0, 30.0

IFN-alpha1

--

G016992

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p22

true true true true

csml-variable:Double

m98717

10

false

infinite

0

unit false false false
TRANSPATHG016992

--

Go back
871.0, 509.0
28.0, 28.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13 p5

true true true true

csml-variable:Double

m24

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
1050.0, 784.0
30.0, 30.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

p14

--

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
729.0, 427.0
32.5, 32.5

MyD88

--

MO000016573

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10 p11 p12

true true true true

csml-variable:Double

m1572

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
870.0, 932.0
29.0, 29.0

IFNalpha1

--

MO000016659

cso30:c:Protein

cso30:i:CC_CellComponent

--

p22

--

true true true true

csml-variable:Double

m1635

10

false

infinite

0

unit false false false
InterProIPR000471
TRANSPATHMO000016659

--

Go back
272.0, 838.0
30.0, 30.0

IL-8

--

MO000017264

cso30:c:Protein

cso30:i:CC_CellComponent

--

p18 p19 p20

--

true true true true

csml-variable:Double

m2120

10

false

infinite

0

unit false false false
InterProIPR002473
TRANSPATHMO000017264

--

Go back
1052.0, 830.0
29.5, 29.5

IL-12

--

MO000017265

cso30:c:Protein

cso30:i:CC_CellComponent

--

p23

--

true true true true

csml-variable:Double

m2121

10

false

infinite

0

unit false false false
TRANSPATHMO000017265

--

Go back
439.0, 233.0
24.0, 24.0

TLR3

--

MO000019398

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1 p17

true true true true

csml-variable:Double

m3965

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000019398

--

Go back
261.0, 131.0
28.0, 28.0

dsRNA

--

MO000022224

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1 p6 p7

true true true true

csml-variable:Double

m119368

10

false

infinite

0

unit false false false
TRANSPATHMO000022224

--

Go back
869.0, 259.0
28.0, 28.0

TRIF

--

MO000041125

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p21

true true true true

csml-variable:Double

m18998

10

false

infinite

0

unit false false false
TRANSPATHMO000041125

--

Go back
521.0, 227.0
28.0, 28.0

dsRNA:TLR3

--

MO000041446

cso30:c:Protein

cso30:i:CC_CellComponent

--

p1

--

true true true true

csml-variable:Double

m19314

10

false

infinite

0

unit false false false
TRANSPATHMO000041446

--

Go back
416.0, 458.0
25.0, 25.0

TLR8

--

MO000042007

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3 p9 p16

true true true true

csml-variable:Double

m19823

10

false

infinite

0

unit false false false
TRANSPATHMO000042007

--

Go back
448.0, 618.0
26.0, 26.0

TLR9

--

MO000042012

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p4

true true true true

csml-variable:Double

m19828

10

false

infinite

0

unit false false false
TRANSPATHMO000042012

--

Go back
404.0, 298.0
26.0, 26.0

TLR7

--

MO000042126

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2 p8 p15

true true true true

csml-variable:Double

m19940

10

false

infinite

0

unit false false false
TRANSPATHMO000042126

--

Go back
559.0, 129.0
24.0, 24.0

Mda-5

--

MO000103999

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m76904

10

false

infinite

0

unit false false false
TRANSPATHMO000103999

--

Go back
323.53107492717163, 73.72235911977702
688.2829744657151, 1013.6040942247341

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
330.16263346258006, 117.28783611981797
667.156972730397, 951.8533409916547

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
414.12764303187754, 230.74714125879433
250.78887982857023, 418.6899095443081

--

e11

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Endosome

--

--

--

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false true false

--

Go back
246.0, 294.5
45.5278310940499, 25.04030710172745

ssRNA

--

e12

cso30:c:Rna

cso30:i:CC_Extracellular

--

--

p2 p3

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
402.5, 333.0
29.72171304782536, 36.39393434427595

ssRNA: TLR7

--

e13

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
414.5, 494.0
28.382602899516744, 34.75420763206132

ssRNA: TLR8

--

e14

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
530.5, 625.0
29.256290618230295, 35.824029328445256

CpG DNA: TLR9

--

e15

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
245.5, 635.125
45.0, 15.75

CpG DNA

--

e16

cso30:c:Dna

cso30:i:CC_Extracellular

--

--

p4

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
414.375, 138.5
24.26933216168717, 37.33743409490334

RIG-1

--

e17

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p6

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
503.375, 170.5
23.25, 45.0

dsRNA: RIG-1

--

e18

cso30:c:Complex

cso30:i:CC_Cytosol

--

p6

--

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
238.5, 418.625
45.0, 24.75

siRNA

--

e19

cso30:c:Rna

cso30:i:CC_Extracellular

--

--

p8 p9

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
323.53107492717163, 73.72235911977702
688.2829744657151, 1013.6040942247341

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
414.625, 413.5
29.139935010831525, 35.68155307448758

SiRNA: TLR7

--

e20

cso30:c:Complex

cso30:i:CC_EndosomeMembrane

--

p8

--

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
410.625, 537.5
28.821488085319114, 35.29161806365605

SiRNA: TLR8

--

e21

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

p9

--

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
561.625, 160.5
26.837318780203294, 32.862022996167305

dsRNA: Mda-5

--

e22

cso30:c:Complex

cso30:i:CC_Cytosol

--

p7

--

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
733.0, 507.0
32.5, 32.5

MyD88{activated}

--

e23

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m23

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
875.0, 557.0
28.0, 28.0

NF-kappaB{activated}

--

e24

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m25

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
529.5, 844.0
34.775086505190316, 18.546712802768166

IL-8

--

e25

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p18 p19 p20

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
247.375, 579.5
28.17452830188679, 30.735849056603776

synthetic RNA

--

e26

cso30:c:RnaOther

cso30:i:CC_Extracellular

--

--

p15 p16 p17

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
412.625, 379.5
25.236918846858856, 30.9023496083986

synthatic RNA: TLR7

--

e27

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
416.6933219463423, 579.5
24.681678053657727, 30.222462922846184

synthetic RNA: TLR8

--

e28

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
416.625, 255.5
27.849816697217136, 34.10181636393934

synthetic RNA: TLR3

--

e29

cso30:c:Complex

cso30:i:CC_EndosomeLumen

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
337.2967344164859, 87.6838480209442
660.7516554870863, 985.6811164224005

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
805.0, 323.0
28.0, 28.0

TRIF{activated}

--

e30

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m31

10

false

infinite

0

unit false false false
TRANSPATHMO000041125

--

Go back
113.5, 383.25
45.0, 25.5

N6-methyaladanosine

--

e31

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p1 p2 p3 p15 p16 p17

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
362.7632044717174, 112.11645359798652
609.8187153766236, 936.8159052683151

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
414.12764303187754, 230.74714125879433
250.78887982857023, 418.6899095443081

--

e5

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeMembrane

--

--

--

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false true false

--

Go back
504.5750683532364, 713.7570537779353
327.4291925473791, 301.1665857628216

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
539.9398600995082, 720.8942640331652
191.45766566085126, 291.8904075565744

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
508.8432328743383, 717.7767310006425
318.8928635051759, 293.1272313174072

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
509.4529706630668, 718.3951428810589
317.673387927718, 291.8904075565744

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
504.5750683532364, 713.7570537779353
327.4291925473791, 301.1665857628216

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
504.5750683532364, 713.7570537779353
327.4291925473791, 301.1665857628216

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
509.4529706630668, 718.3951428810589
317.673387927718, 291.8904075565744

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
743.5922815349356, 837.4394298612297
20.455976889327896, 18.78147874855491

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
689.935356126799, 924.0170931195355
57.92508992923839, 53.18342171581657

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
504.5750683532364, 713.7570537779353
327.4291925473791, 301.1665857628216

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
414.12764303187754, 230.74714125879433
250.78887982857023, 418.6899095443081

--

e6

cso30:c:EntityBiologicalCompartment

cso30:i:CC_EndosomeLumen

--

--

--

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false true false

--

Go back
581.7482867193967, 847.5929959309482
10.369201421314353, 5.063602571393214

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
581.4020297330685, 832.4921348178977
35.49134109864954, 64.79322965948421

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
596.2910801451853, 874.6340728078062
5.540111781252605, 5.618925065321121

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
332.5741092936376, 105.87418988716927
674.9911643051797, 970.051372072972

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
334.98558512469526, 122.99465923614225
647.5270669576745, 953.5846599999352

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
341.41618734084886, 140.11512858511526
644.5707507061458, 941.0786361307315

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
330.0, 184.0
25.0, 25.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c70 : 1
stoichiometry:c3 : 1

m119368*m3965*0.1

nodelay

--

true

0

false

PMID: 16111629, 11607032, 14729660 TLR3 recognizes dsRNA derived from virus or host mRNA. PMID: 16111629 Overall, these new data strongly suggest that TLR3, TLR7, and TLR8 recognize ¡Èunmethylated RNA,¡É similar to TLR9 recognition of unmethylated CpG motifs in DNA. PMID: 16111629 Conversely, modification of stimulatory RNA with N6-methyaladanosine, which destabilizes RNA duplexes, abrogates TLR3-mediated immune activations.

Go back
666.0, 428.0
30.0, 30.0

p10

p10

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c31 : 1
stoichiometry:c26 : 1

m1572*m13*0.1

nodelay

--

true

0

false

PMID: 16111629 Currently known innate recognitions are shown in this graphic, including receptors, adaptors, signal transductions, and transcriptions.

Go back
666.0, 468.0
30.0, 30.0

p11

p11

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c32 : 1
stoichiometry:c28 : 1

m1572*m14*0.1

nodelay

--

true

0

false

PMID: 16111629 Currently known innate recognitions are shown in this graphic, including receptors, adaptors, signal transductions, and transcriptions.

Go back
665.0, 507.0
27.0, 27.0

p12

p12

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c29 : 1
stoichiometry:c33 : 1
stoichiometry:c30 : 1

m1572*m15*0.1

nodelay

--

true

0

false

PMID: 16111629 Currently known innate recognitions are shown in this graphic, including receptors, adaptors, signal transductions, and transcriptions.

Go back
802.0, 508.0
29.0, 29.0

p13

p13

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c34 : 1
stoichiometry:c36 : 1
stoichiometry:c35 : 1

m24*m23*0.1

nodelay

--

true

0

false

PMID: 16111629 Currently known innate recognitions are shown in this graphic, including receptors, adaptors, signal transductions, and transcriptions.

Go back
870.0, 784.0
30.0, 30.0

p14

p14

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c39 : 1
stoichiometry:c38 : 1

m25*m93309*0.1

nodelay

--

true

0

false

PMID: 16111629 First, the authors observed that among natural RNA, lipofection of bacterial, but not mammalian, RNA (with an exception of mitochondrial RNA) activated human myeloid dendritic cells (DCs) to secrete TNFalpha.

Go back
316.0, 382.0
25.0, 25.0

p15

p15

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c40 : 1
stoichiometry:c41 : 1
stoichiometry:c75 : 1
stoichiometry:c42 : 1

m27*m19940*0.1

nodelay

--

true

0

false

PMID: 16111629 Synthetic ssRNAs of different sequences and lengths could activate TLR3-, TLR7-, and TLR8-expressing cells to secrete IL-8, an activity that was severely impaired when modified nucleosides such as N6-methyaladanosine, 5-methylcytidine, 2-thiouridine, or pseudouridine were introduced into the RNA.

Go back
325.0, 583.0
23.0, 23.0

p16

p16

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c44 : 1
stoichiometry:c74 : 1
stoichiometry:c45 : 1

m19823*m27*0.1

nodelay

--

true

0

false

PMID: 16111629 Synthetic ssRNAs of different sequences and lengths could activate TLR3-, TLR7-, and TLR8-expressing cells to secrete IL-8, an activity that was severely impaired when modified nucleosides such as N6-methyaladanosine, 5-methylcytidine, 2-thiouridine, or pseudouridine were introduced into the RNA.

Go back
324.0, 262.0
21.0, 21.0

p17

p17

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c47 : 1
stoichiometry:c71 : 1
stoichiometry:c48 : 1

m3965*m27*0.1

nodelay

--

true

0

false

PMID: 16111629 Synthetic ssRNAs of different sequences and lengths could activate TLR3-, TLR7-, and TLR8-expressing cells to secrete IL-8, an activity that was severely impaired when modified nucleosides such as N6-methyaladanosine, 5-methylcytidine, 2-thiouridine, or pseudouridine were introduced into the RNA.

Go back
405.0, 839.0
27.0, 27.0

p18

p18

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c52 : 1
stoichiometry:c49 : 1

m26*m28*0.1

nodelay

--

true

0

false

PMID: 16111629 Synthetic ssRNAs of different sequences and lengths could activate TLR3-, TLR7-, and TLR8-expressing cells to secrete IL-8, an activity that was severely impaired when modified nucleosides such as N6-methyaladanosine, 5-methylcytidine, 2-thiouridine, or pseudouridine were introduced into the RNA.

Go back
406.0, 788.0
25.0, 25.0

p19

p19

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c56 : 1
stoichiometry:c54 : 1

m30*m26*0.1

nodelay

--

true

0

false

PMID: 16111629 Synthetic ssRNAs of different sequences and lengths could activate TLR3-, TLR7-, and TLR8-expressing cells to secrete IL-8, an activity that was severely impaired when modified nucleosides such as N6-methyaladanosine, 5-methylcytidine, 2-thiouridine, or pseudouridine were introduced into the RNA.

Go back
320.0, 298.0
25.0, 25.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c72 : 1
stoichiometry:c6 : 1

m19940*m12*0.1

nodelay

--

true

0

false

PMID: 16111629, 14976262, 14976261 TLR7 and TLR8 have recently been shown to recognize viral or synthetic single-stranded (ss) RNA. PMID: 16111629 Overall, these new data strongly suggest that TLR3, TLR7, and TLR8 recognize ¡Èunmethylated RNA,¡É similar to TLR9 recognition of unmethylated CpG motifs in DNA. PMID: 16111629 Furthermore, N6-methyaladanosine, found in many viral RNAs, also diminishes TLR7- and TLR8-mediated RNA recognition, implying that such modification is ideal for viral evasion of TLR-mediated immune responses, as the authors discuss.

Go back
408.0, 882.0
27.0, 27.0

p20

p20

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c57 : 1
stoichiometry:c55 : 1

m29*m26*0.1

nodelay

--

true

0

false

PMID: 16111629 Synthetic ssRNAs of different sequences and lengths could activate TLR3-, TLR7-, and TLR8-expressing cells to secrete IL-8, an activity that was severely impaired when modified nucleosides such as N6-methyaladanosine, 5-methylcytidine, 2-thiouridine, or pseudouridine were introduced into the RNA.

Go back
805.0, 259.0
27.0, 27.0

p21

p21

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c60 : 1
stoichiometry:c59 : 1

m18998*m30*0.1

nodelay

--

true

0

false

PMID: 16111629 Currently known innate recognitions are shown in this graphic, including receptors, adaptors, signal transductions, and transcriptions.

Go back
872.0, 874.0
26.0, 26.0

p22

p22

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c65 : 1
stoichiometry:c66 : 1
stoichiometry:c64 : 1

m98717*m31*0.1

nodelay

--

true

0

false

PMID: 16111629 Finally, unmodified, but not modified, RNA potently activated in vitro generated or freshly isolated human DCs, leading to production of IL-12 and IFNalpha as well as the enhanced expression of costimulatory molecules.

Go back
912.0, 830.0
29.0, 29.0

p23

p23

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c69 : 1
stoichiometry:c67 : 1

m93589*m25*0.1

nodelay

--

true

0

false

PMID: 16111629 Finally, unmodified, but not modified, RNA potently activated in vitro generated or freshly isolated human DCs, leading to production of IL-12 and IFNalpha as well as the enhanced expression of costimulatory molecules.

Go back
321.0, 459.0
23.0, 23.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c73 : 1
stoichiometry:c9 : 1

m19823*m12*0.1

nodelay

--

true

0

false

PMID: 16111629, 14976262, 14976261 TLR7 and TLR8 have recently been shown to recognize viral or synthetic single-stranded (ss) RNA. PMID: 16111629 Overall, these new data strongly suggest that TLR3, TLR7, and TLR8 recognize ¡Èunmethylated RNA,¡É similar to TLR9 recognition of unmethylated CpG motifs in DNA. PMID: 16111629 Furthermore, N6-methyaladanosine, found in many viral RNAs, also diminishes TLR7- and TLR8-mediated RNA recognition, implying that such modification is ideal for viral evasion of TLR-mediated immune responses, as the authors discuss.

Go back
331.0, 630.0
25.0, 25.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c11 : 1
stoichiometry:c12 : 1

m19828*m16*0.1

nodelay

--

true

0

false

PMID: 16111629 Overall, these new data strongly suggest that TLR3, TLR7, and TLR8 recognize ¡Èunmethylated RNA,¡É similar to TLR9 recognition of unmethylated CpG motifs in DNA.

Go back
805.0, 467.0
27.0, 27.0

p5

p5

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c63 : 1
stoichiometry:c62 : 1

m24*m31*0.1

nodelay

--

true

0

false

PMID: 16111629 Currently known innate recognitions are shown in this graphic, including receptors, adaptors, signal transductions, and transcriptions.

Go back
330.0, 144.0
25.0, 25.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c14 : 1
stoichiometry:c15 : 1

m119368*m17*0.1

nodelay

--

true

0

false

PMID: 16111629 It will be of interest to learn whether such modifications of RNA have an impact on TLR-independent innate recognition of RNA within cells through molecules such as RIG-I and MDA-5 and, of course, what the physiological relevance of their findings is to infectious diseases as well as to immunological disorders associated with RNA-induced immunomodulation.

Go back
362.0, 96.0
25.0, 25.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c23 : 1
stoichiometry:c24 : 1

m119368*m76904*0.1

nodelay

--

true

0

false

PMID: 16111629 It will be of interest to learn whether such modifications of RNA have an impact on TLR-independent innate recognition of RNA within cells through molecules such as RIG-I and MDA-5 and, of course, what the physiological relevance of their findings is to infectious diseases as well as to immunological disorders associated with RNA-induced immunomodulation.

Go back
321.0, 419.0
23.0, 23.0

p8

p8

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c20 : 1
stoichiometry:c16 : 1

m19940*m19*0.1

nodelay

--

true

0

false

PMID: 16111629, 14976262, 14976261 TLR7 and TLR8 have recently been shown to recognize viral or synthetic single-stranded (ss) RNA.

Go back
324.0, 542.0
25.0, 25.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c18 : 1
stoichiometry:c21 : 1

m19*m19823*0.1

nodelay

--

true

0

false

PMID: 16111629, 14976262, 14976261 TLR7 and TLR8 have recently been shown to recognize viral or synthetic single-stranded (ss) RNA.

Go back
289.0, 156.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
363.9531557045556, 632.0

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
291.0, 643.0

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
356.0, 643.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
289.0, 148.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
363.0, 157.0

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
355.0, 160.0

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
344.0, 431.0

c16

c16

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
269.0, 443.0

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
354.9155238698951, 483.0

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
345.6107633501415, 324.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
362.28886338270684, 205.2973429588436

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
284.0, 431.0

c20

c20

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
349.0, 555.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
289.0, 116.6841502903183

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
394.89605815944407, 112.28540481665368

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
387.0, 113.0

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
704.0, 443.0

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
694.0, 458.0

c26

c26

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
702.7492919018569, 453.0

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
696.0, 492.0

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
696.1849490362268, 460.0

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
355.0, 200.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
692.0, 522.0

c30

c30

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
432.0, 356.0

c31

c31

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
443.0, 485.85604314135145

c32

c32

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
560.0, 539.3981535963595

c33

c33

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
839.0, 523.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
831.0, 532.0

c35

c35

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
766.0, 523.0

c36

c36

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
885.1607715451005, 585.0

c37

c37

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
900.0, 799.0

c38

c38

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
764.0, 799.0

c39

c39

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
353.0, 311.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
266.0, 414.5717776526593

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
346.7931034482759, 323.0

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
341.0, 395.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
350.7587440432824, 483.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
276.0, 595.0

c44

c44

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
348.0, 595.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
352.77076811902384, 248.0

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
215.24761076084968, 273.0274085050628

c47

c47

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
345.0, 273.0

c48

c48

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
310.0, 853.0

c49

c49

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
292.0, 308.0

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
440.0, 853.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
198.6646006426775, 237.00951711916525

c51

c51

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
174.81081524889544, 340.50039115978973

c52

c52

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
215.33682759161377, 597.0

c53

c53

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
309.44252738599823, 806.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
309.6177225322558, 860.4434204348745

c55

c55

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
438.4174343087949, 808.9969431550686

c56

c56

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
442.5570469020753, 859.0

c57

c57

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
840.0, 273.0

c58

c58

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
819.0, 286.0

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
345.0, 317.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
444.0, 273.0

c60

c60

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
838.735033111711, 493.31732891776346

c61

c61

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
829.0, 494.0

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
819.0, 351.0

c63

c63

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
885.0, 900.0

c64

c64

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
784.0, 887.0

c65

c65

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
833.0, 336.5332850199809

c66

c66

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
941.0, 845.0

c67

c67

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
766.0, 845.0

c68

c68

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
891.0, 585.0

c69

c69

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
352.0, 471.0

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
136.0, 196.3860582294717

c70

c70

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
137.0, 251.54990048485814

c71

c71

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
159.0, 318.57567719431665

c72

c72

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
138.0, 409.0

c73

c73

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
135.57772843784113, 409.0

c74

c74

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
159.0, 395.0254771902119

c75

c75

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
274.0, 320.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
344.0, 476.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back