mRNA Processing (Homo sapiens)

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1degradedPoly(A)pb IIU1 snRNPSR-repressor proteinsAGhnRNP regulatorsU4 snRNPexon 1SR-proteinsPolr2aFormation of the Spliceosomal E complexhnRNPs5'mRNA polyadenylation3'exon 15'Additional FactorsFormation of pre-mRNPsSR-phosphatasesYYYYsnRNP Sm core complexexon 1(3)5'U2 snRNPAccessory ProteinsFormation of pre-mRNPs(1)Poly(A) polymerase alphaCF IILariat Formation and 5'-Splice Site CleavageFormation of the Spliceosomal A complexpre-mRNA5'AAUAAACF I3'YYYYPoly(A)-binding protein II35AAdditional FactorsAexon 1snRNP Sm core complexSR-binding sitesUGCPSFSerine/Argenine Rich Proteins(SR)Formation of the Spliceosomal C complexFormation of the Spliceosomal B complexAdditional FactorsU4CstFPutative Alternative SplicingRegulatorsU1 snRNPintronmRNA splice site selectionU2AFU1CAAP-mRNA splicing (major pathway)Cleavage of mRNA at the 3'-endexon 2U2AF(2)5' G capSF3b14bPoly(A) polAG3'Primary RNA transcript3'YYYYSR-kinasesMethylation of mRNAexon 2(2b)Regulation ofAlternative SplicingU6YYYYU4:U5:U6 tri-snRNP complexU53'AGInternal methylation of mRNAFormation of the Spliceosomal B complexU2 snRNPsSpt5(2c)Internal methylation of mRNAU2 snRNPGUFormation of the active Spliceosomal C complex3'3'Formation of the Spliceosomal A complexAGU6 snRNPAsplicing factor SF3B5'exon 1AG3'5'U2SR-binding sitesheterogeneous nuclear ribonucleoproteins3'PSR-proteinsRNA helicase AU5 snRNPRngtt (capping enzyme)5'Pi5'splicesome associated helicasesmRNA 3'-end processingRNAi pathwayUG65Rnmt (methyltransferase)mRNA cappingexon 2iPoACap Binding(2a)Note: New participating members shown at each stepRNA helicaseAGU4/U6snRNP Sm core complex5'exon 2mRNA CappingYYYYSR-proteinsProcessing of Intron-Containing Pre-mRNAKinases Phosphorylating RS domains?exon 2YYYYCleavage at the 3'-Splice-Site and Exon Ligation5'3'Formation of the Spliceosomal E complexCFIMisc.exon 1U5CPSFSR protein kinasesAAdditional SR proteinsSR protein phosphatasesCF IIright click on blue text for detailed informationexon 23'splicing factor SF3ACstFAAAAAAA5'RNU2HNRPRSF3B1LSM7SNRPB2DHX9DICER1SNRP70PPM1GPCBP2FUSNCBP2CDC40CLK4CSTF3SF3B4SFRS14SUPT5HSNRPA1RNPC2PRPF18SNRPALSM2SFRS6HRMT1L1WDR57SFRS2PTBP2CLK1SF3A3DDX1SSFA1PRPF8U5 snRNARNGTTCDC40NUDT21HNRPLSFRS10HNRPA1PTBP1SFRS12HNRPDCSTF1NSEP1NXF1SNRPD2SFRS5SNRPD1PRPF4HNRPH1CUGBP1HRMT1L2DHX16RNMTCUGBP2CPSF4U4 snRNAPAPOLAHNRPUTMP21C20orf14U2AF1RBMXFUSIP1FUSIP1RBM17PHF5ACPSF1GMPSF3B3CD2BP2HNRPA3P1POLR2AU5-116KDDHX38SF3A2SFRS7HNRPABSFRS8DHX8RNPS1SF4U2AF2DHX15SRPK1XRN2RBM5SRP54SFPQATPSNRPNSFRS4SNRPGSF3B5SPOPSSFA1SNRPEFNBP3SNRPNHNRPA2B1SNRPBHNRPH2PRPF8DNAJC8NCBP1SF3B2SFRS16PSKH1HNRPMSRPK2PRPF4BCLK3DDX20NONOLSM2SMC1L1PRPF4METTL3SRRM1BRUNOL4CPSF3PRPF3CSTF2SFRS1HNRPCSF3A1SFRS9SFRS3SNRPD3PABPN1HEABCLK2TXNL4ASSFA1U1 snRNACSTF2TRnu6CPSF2SNRPFHNRPK


This process describes the conversion of precursor messenger RNA into mature messenger RNA (mRNA).

The pre-mRNA molecule undergoes three main modifications. These modifications are 5' capping, 3' polyadenylation, and RNA splicing, which occur in the cell nucleus before the RNA is translated.

5' Capping: Capping of the pre-mRNA involves the addition of 7-methylguanosine (m7G) to the 5' end. The cap protects the 5' end of the primary RNA transcript from attack by ribonucleases that have specificity to the 3'5' phosphodiester bonds.

3' Processing: The pre-mRNA processing at the 3' end of the RNA molecule involves cleavage of its 3' end and then the addition of about 200 adenine residues to form a poly(A) tail. As the poly(A) tails is synthesised, it binds multiple copies of poly(A) binding protein, which protects the 3'end from ribonuclease digestion.

Splicing: RNA splicing is the process by which introns, regions of RNA that do not code for protein, are removed from the pre-mRNA and the remaining exons connected to re-form a single continuous molecule.

Description adapted from Wikipedia:

Pathway adapted from

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Ontology Terms



  1. Carmody SR, Wente SR; ''mRNA nuclear export at a glance.''; J Cell Sci, 2009 PubMed Europe PMC Scholia


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105857view23:19, 15 August 2019KhanspersModified description
102226view21:19, 11 December 2018Khanspersreplaced arcs with curved graphical lines
96893view13:50, 18 April 2018FehrhartFixed minor graphical issues
96288view21:54, 6 March 2018Andrewlmasonnone
95128view15:26, 16 November 2017Mkutmonremoved nested groups
94839view15:55, 6 October 2017Khanspersconverted interactions to graphical lines
79980view14:12, 29 April 2015Zarireplaced new Id for SSFA1
71369view18:37, 17 October 2013MaintBotAutomated update of data sources
70024view01:52, 12 July 2013AlexanderPicoModified title
68926view17:33, 8 July 2013MaintBotUpdated to 2013 gpml schema
67498view11:09, 26 June 2013DdiglesOntology Term : 'spliceosome pathway' added !
45374view21:22, 7 October 2011Khansperscleaned up description and removed old comment
44924view10:51, 6 October 2011MartijnVanIerselOntology Term : 'transcription pathway' added !
41073view23:19, 1 March 2011MaintBotRemoved redundant pathway information and comments
38901view20:24, 24 September 2010AlexanderPicominor tweaks
38872view18:29, 24 September 2010Khanspers
35228view18:39, 11 February 2010KhanspersChanged snRNAs from Other to RNA
35227view18:35, 11 February 2010KhanspersPeriodical save, work in progress
35226view18:21, 11 February 2010KhanspersModified description
35225view18:20, 11 February 2010KhanspersModified description
35122view13:25, 11 February 2010MartijnVanIerseladded lit. ref.
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21548view11:32, 14 November 2008MaintBot[[Pathway:Homo sapiens:mRNA processing Reactome]] moved to [[Pathway:WP411]]: Moved to stable identifier
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External references


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NameTypeDatabase referenceComment
ATPMetabolite1927-31-7 (CAS)
BRUNOL4GeneProduct56853 (Entrez Gene)
C20orf14GeneProduct24148 (Entrez Gene)
CD2BP2GeneProduct10421 (Entrez Gene)
CDC40GeneProduct51362 (Entrez Gene)
CLK1GeneProduct1195 (Entrez Gene) PMID: 15010457: Inhibitor John C. Bell, PhD

Professor, Depts. of Medicine and Biochemistry, Microbiology & Immunology University of Ottawa Career Scientist, Ottawa Regional Cancer Centre Associate Scientist, The Ottawa Hospital Research Institute Telephone: 613-737-7700 ext 6893 Fax: 613-247-3524 Email: The control of pre-mRNA splicing by the Clk kinase family

We are studying a family of kinases which we believe provide an interface between intracellular signaling networks and the post-transcriptional mechanism of mRNA splicing. We are performing a structure:function analysis of the three Clk family members to identify domains in the three proteins which are involved in regulating splicing. Using homologous recombination we are generating null strains of mice which are lacking one, two or all three Clk genes. The Clk kinases all possess dual specificity kinase activity and yeast expression systems are being used to produce large amounts of the kinase to perform a detailed analysis of the sites of serine, threonine and tyrosine autophosphorylation within the kinase.
CLK2GeneProduct1196 (Entrez Gene)
CLK3GeneProduct1198 (Entrez Gene)
CLK4GeneProduct57396 (Entrez Gene)
CPSF1GeneProduct29894 (Entrez Gene)
CPSF2GeneProduct53981 (Entrez Gene)
CPSF3GeneProduct51692 (Entrez Gene)
CPSF4GeneProduct10898 (Entrez Gene)
CSTF1GeneProduct1477 (Entrez Gene)
CSTF2GeneProduct1478 (Entrez Gene)
CSTF2TGeneProduct23283 (Entrez Gene)
CSTF3GeneProduct1479 (Entrez Gene)
CUGBP1GeneProduct10658 (Entrez Gene)
CUGBP2GeneProduct10659 (Entrez Gene)
DDX1GeneProduct1653 (Entrez Gene)
DDX20GeneProduct11218 (Entrez Gene)
DHX15GeneProduct1665 (Entrez Gene)
DHX16GeneProduct8449 (Entrez Gene)
DHX38GeneProduct9785 (Entrez Gene)
DHX8GeneProduct1659 (Entrez Gene)
DHX9GeneProduct1660 (Entrez Gene)
DICER1GeneProduct23405 (Entrez Gene)
DNAJC8GeneProduct22826 (Entrez Gene)
FNBP3GeneProduct55660 (Entrez Gene)
FUSGeneProduct2521 (Entrez Gene)
FUSIP1GeneProduct10772 (Entrez Gene)
GMPMetabolite85-32-5 (CAS)
HEABGeneProduct10978 (Entrez Gene)
HNRPA1GeneProduct3178 (Entrez Gene)
HNRPA2B1GeneProduct3181 (Entrez Gene)
HNRPA3P1GeneProduct10151 (Entrez Gene)
HNRPABGeneProduct3182 (Entrez Gene)
HNRPCGeneProduct3183 (Entrez Gene)
HNRPDGeneProduct3184 (Entrez Gene)
HNRPH1GeneProduct3187 (Entrez Gene)
HNRPH2GeneProduct3188 (Entrez Gene)
HNRPKGeneProduct3190 (Entrez Gene)
HNRPLGeneProduct3191 (Entrez Gene)
HNRPMGeneProduct4670 (Entrez Gene)
HNRPRGeneProduct10236 (Entrez Gene)
HNRPUGeneProduct3192 (Entrez Gene)
HRMT1L1GeneProduct3275 (Entrez Gene)
HRMT1L2GeneProduct3276 (Entrez Gene)
LSM2GeneProduct57819 (Entrez Gene)
LSM7GeneProduct51690 (Entrez Gene)
METTL3GeneProduct56339 (Entrez Gene)
NCBP1GeneProduct4686 (Entrez Gene)
NCBP2GeneProduct22916 (Entrez Gene)
NONOGeneProduct4841 (Entrez Gene)
NSEP1GeneProduct4904 (Entrez Gene)
NUDT21GeneProduct11051 (Entrez Gene)
NXF1GeneProduct10482 (Entrez Gene)
PABPN1GeneProduct8106 (Entrez Gene)
PAPOLAGeneProduct10914 (Entrez Gene)
PCBP2GeneProduct5094 (Entrez Gene)
PHF5AGeneProduct84844 (Entrez Gene)
POLR2AGeneProduct5430 (Entrez Gene)
PPM1GGeneProduct5496 (Entrez Gene) PMID: 12773558
PRPF18GeneProduct8559 (Entrez Gene)
PRPF3GeneProduct9129 (Entrez Gene)
PRPF4GeneProduct9128 (Entrez Gene)
PRPF4BGeneProduct8899 (Entrez Gene)
PRPF8GeneProduct10594 (Entrez Gene)
PSKH1GeneProduct5681 (Entrez Gene) PMID: 12466556
PTBP1GeneProduct5725 (Entrez Gene)
PTBP2GeneProduct58155 (Entrez Gene)
RBM17GeneProduct84991 (Entrez Gene)
RBM5GeneProduct10181 (Entrez Gene)
RBMXGeneProduct27316 (Entrez Gene)
RNGTTGeneProduct8732 (Entrez Gene)
RNMTGeneProduct8731 (Entrez Gene)
RNPC2GeneProduct9584 (Entrez Gene)
RNPS1GeneProduct10921 (Entrez Gene) PMID: 14729963
RNU2GeneProduct6066 (Entrez Gene) GenBank sequence: K00027
Rnu6RnaGenBank sequence: M10329
SF3A1GeneProduct10291 (Entrez Gene)
SF3A2GeneProduct8175 (Entrez Gene)
SF3A3GeneProduct10946 (Entrez Gene)
SF3B1GeneProduct23451 (Entrez Gene)
SF3B2GeneProduct10992 (Entrez Gene)
SF3B3GeneProduct23450 (Entrez Gene)
SF3B4GeneProduct10262 (Entrez Gene)
SF3B5GeneProduct83443 (Entrez Gene)
SF4GeneProduct57794 (Entrez Gene) inferred from: SURP 2, G patch protein, UniProt:O60378
SFPQGeneProduct6421 (Entrez Gene)
SFRS10GeneProduct6434 (Entrez Gene)
SFRS12GeneProduct140890 (Entrez Gene) PMID: 14559993. SRrp86 is a unique member of the SR protein superfamily containing one RNA recognition motif and two serine-arginine (SR)-rich domains separated by an unusual glutamic acid-lysine (EK)-rich region. Previously, we showed that SRrp86 could regulate alternative splicing by both positively and negatively modulating the activity of other SR proteins and that the unique EK domain could inhibit both constitutive and alternative splicing. These functions were most consistent with the model in which SRrp86 functions by interacting with and thereby modulating the activity of target proteins. To identify the specific proteins that interact with SRrp86, we used a yeast two-hybrid library screen and immunoprecipitation coupled to mass spectrometry. We show that SRrp86 interacts with all of the core SR proteins, as well as a subset of other splicing regulatory proteins, including SAF-B, hnRNP G, YB-1, and p72. In contrast to previous results that showed activation of SRp20 by SRrp86, we now show that SAF-B, hnRNP G, and 9G8 all antagonize the activity of SRrp86. Overall, we conclude that not only does SRrp86 regulate SR protein activity but that it is, in turn, regulated by other splicing factors to control alternative splice site selection.
SFRS14GeneProduct10147 (Entrez Gene)
SFRS16GeneProduct11129 (Entrez Gene)
SFRS1GeneProduct6426 (Entrez Gene) Antagonist splicing factor
SFRS2GeneProduct6427 (Entrez Gene)
SFRS3GeneProduct6428 (Entrez Gene)
SFRS4GeneProduct6429 (Entrez Gene)
SFRS5GeneProduct6430 (Entrez Gene)
SFRS6GeneProduct6431 (Entrez Gene)
SFRS7GeneProduct6432 (Entrez Gene)
SFRS8GeneProduct6433 (Entrez Gene)
SFRS9GeneProduct8683 (Entrez Gene) PMID: 12738786, PMID: 12024014 (associated with hnRNP A1 splicing)
SMC1L1GeneProduct8243 (Entrez Gene)
SNRP70GeneProduct6625 (Entrez Gene)
SNRPA1GeneProduct6627 (Entrez Gene)
SNRPAGeneProduct6626 (Entrez Gene)
SNRPB2GeneProduct6629 (Entrez Gene)
SNRPBGeneProduct6628 (Entrez Gene)
SNRPD1GeneProduct6632 (Entrez Gene)
SNRPD2GeneProduct6633 (Entrez Gene)
SNRPD3GeneProduct6634 (Entrez Gene)
SNRPEGeneProduct6635 (Entrez Gene)
SNRPFGeneProduct6636 (Entrez Gene)
SNRPGGeneProduct6637 (Entrez Gene)
SNRPNGeneProduct6638 (Entrez Gene)
SPOPGeneProduct8405 (Entrez Gene)
SRP54GeneProduct6729 (Entrez Gene) PMID: 14729963
SRPK1GeneProduct6732 (Entrez Gene) PMID: 12773558
SRPK2GeneProduct6733 (Entrez Gene) PMID: 12773558
SRRM1GeneProduct10250 (Entrez Gene)
SSFA1GeneProduct4809 (Entrez Gene)
SUPT5HGeneProduct6829 (Entrez Gene)
TMP21GeneProduct10972 (Entrez Gene)
TXNL4AGeneProduct10907 (Entrez Gene)
U1 snRNARnaGenBank sequence: J00645
U2AF1GeneProduct7307 (Entrez Gene)
U2AF2GeneProduct11338 (Entrez Gene)
U4 snRNARnaGenBank sequence: M10328, M18004
U5 snRNARnaGenBank sequence: AB021173
U5-116KDGeneProduct9343 (Entrez Gene)
WDR57GeneProduct9410 (Entrez Gene)
XRN2GeneProduct22803 (Entrez Gene)

Annotated Interactions

No annotated interactions

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