mRNA Processing (Homo sapiens)

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1Formation of the Spliceosomal B complex(2b)3'AGU4SR-binding sitesCFIGU3'exon 2intronpre-mRNAU2 snRNPYYYYPolr2aFormation of the active Spliceosomal C complexsplicing factor SF3AU4/U65'mRNA splicing (major pathway)Spt5Poly(A)pb IIexon 1(1)Rnmt (methyltransferase)snRNP Sm core complexU4 snRNPsnRNP Sm core complexPrimary RNA transcript(2c)YYYYSR-phosphatasesU2U2 snRNPsFormation of pre-mRNPsACleavage at the 3'-Splice-Site and Exon LigationFormation of the Spliceosomal B complex5'Cleavage of mRNA at the 3'-end(2a)CF IIPoly(A)-binding protein IISR-proteins5'CPSFAG3'exon 2U6 snRNPAccessory Proteins5'Cap BindingAdditional SR proteinsSR protein kinasesKinases Phosphorylating RS domains?U1exon 2UGAG3'5'CA3'CF IISR protein phosphatasesCPSFAU1 snRNP5'SR-repressor proteinsAdditional FactorsRNA helicase ARNA helicaseRegulation ofAlternative SplicingU5SR-kinasesYYYYAP-3'YYYYMisc.SR-binding sitesU2 snRNPAPiCstFheterogeneous nuclear ribonucleoproteins5'splicing factor SF3BPoly(A) polhnRNPsA3'5' G capexon 1CstFAG3'mRNA cappingU2AF(2)Formation of the Spliceosomal A complex35AAUAAARngtt (capping enzyme)Putative Alternative SplicingRegulatorsU53'mRNA Cappingright click on blue text for detailed informationU2AFFormation of the Spliceosomal A complexU6exon 1(3)exon 1UGMethylation of mRNAmRNA splice site selectionLariat Formation and 5'-Splice Site CleavagePoly(A) polymerase alphaProcessing of Intron-Containing Pre-mRNAexon 1AGFormation of the Spliceosomal E complexYYYYAdditional Factors65ARNAi pathway5'SF3b14bInternal methylation of mRNAiPo5'exon 2exon 2splicesome associated helicases3'Formation of pre-mRNPsAG5'U4:U5:U6 tri-snRNP complexU1 snRNPPAAAAAAAsnRNP Sm core complexSR-proteinsmRNA polyadenylationmRNA 3'-end processingU5 snRNPInternal methylation of mRNAYYYYhnRNP regulatorsSerine/Argenine Rich Proteins(SR)exon 1CF ISR-proteins5'3'Formation of the Spliceosomal E complexdegradedexon 2Note: New participating members shown at each stepFormation of the Spliceosomal C complexAdditional FactorsSF3A1SSFA1BRUNOL4SRPK2LSM7CDC40SFRS8DHX8HNRPCSFRS10NCBP2SNRPD2SNRP70NONOSFRS16SFRS4SNRPGHEABRNGTTDHX15HNRPLSNRPD3RNPS1PRPF3PRPF18SRPK1DHX38HNRPH1RNPC2PRPF4HNRPA3P1PAPOLACLK1HNRPDRnu6U5-116KDSFRS12SFRS14SUPT5HSF3B5ATPGMPDICER1DHX9FNBP3SSFA1HNRPA1CSTF1DHX16SFRS5SNRPA1SFRS6CD2BP2HNRPA2B1SNRPBHNRPRLSM2DNAJC8POLR2AU2AF1NUDT21SF3B3SSFA1TXNL4APPM1GHNRPABRBM17SNRPD1SFRS9CSTF2HRMT1L1WDR57CPSF1PRPF4BCPSF4FUSPRPF8HNRPMSNRPERNU2FUSIP1LSM2SNRPB2SRRM1HNRPKCUGBP2FUSIP1SNRPFU1 snRNARNMTSFRS7SNRPNPRPF8U4 snRNASF4C20orf14HNRPH2SMC1L1HNRPUDDX20NSEP1NCBP1DDX1SF3B1XRN2PTBP2PRPF4U5 snRNAHRMT1L2PCBP2PHF5ASRP54METTL3SNRPACSTF2TPTBP1SFRS2CDC40RBM5RBMXSNRPNPABPN1CSTF3CLK2NXF1SF3A3CPSF2PSKH1TMP21SF3A2SFRS3SF3B2CLK4CLK3SFRS1CPSF3U2AF2SPOPSF3B4SFPQCUGBP1


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

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal.

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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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