mRNA Processing (Homo sapiens)

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1AGAAAAAAAUGYYYYCF I5heterogeneous nuclear ribonucleoproteins(2a)3PiSR protein phosphatases5Putative Alternative SplicingRegulatorsFormation of pre-mRNPs(3)Regulation ofAlternative Splicing(2)Additional Factorsintronsplicing factor SF3APoly(A)pb IICap BindingAexon 1exon 1YYYYU2AFRngtt (capping enzyme)CstFexon 2RNAi pathwayFormation of the Spliceosomal E complexPoly(A)-binding protein IICleavage of mRNA at the 3'-endU6 snRNPPoly(A) polSR-binding sitesU2 snRNPmRNA 3'-end processing5Serine/Argenine Rich Proteins(SR)U2 snRNPshnRNP regulators(2b)CPSFAGmRNA splice site selection65AGmRNA polyadenylationSR protein kinases5 G cap3(1)5exon 1AGexon 2hnRNPsmRNA splicing (major pathway)3exon 2Additional FactorsA(2c)CFISR-proteinsAdditional FactorssnRNP Sm core complexACleavage at the 3'-Splice-Site and Exon Ligation5U2mRNA capping3Formation of the Spliceosomal C complexU4/U6SR-kinasesCF IIU1U4exon 1SR-binding sites5RNA helicaseMisc.5YYYY5Formation of the Spliceosomal E complexYYYYSpt5snRNP Sm core complexpre-mRNASR-proteins33right click on blue text for detailed informationmRNA Capping5Poly(A) polymerase alphaAccessory ProteinsU1 snRNPsplicing factor SF3BPolr2aU1 snRNP5Lariat Formation and 5'-Splice Site CleavageSF3b14bexon 2exon 2AAUAAAFormation of the Spliceosomal B complexU5 snRNPAdditional SR proteinsU2 snRNPsnRNP Sm core complexexon 1U6SR-proteinsNote: New participating members shown at each stepCPSFiPosplicesome associated helicasesAU4:U5:U6 tri-snRNP complex3Kinases Phosphorylating RS domains?SR-repressor proteinsProcessing of Intron-Containing Pre-mRNAGUUGRnmt (methyltransferase)SR-phosphatases335U5exon 1U2AF5CstFP-exon 2CF IIPrimary RNA transcriptAGFormation of the Spliceosomal A complex3Internal methylation of mRNAFormation of the Spliceosomal B complexFormation of the Spliceosomal A complex3degradedU5Methylation of mRNAInternal methylation of mRNAAAGFormation of the active Spliceosomal C complexRNA helicase APU4 snRNPYYYYFormation of pre-mRNPsCAYYYY3AU1 snRNASF3A2PAPOLAHNRPH2PRPF4SFRS5HNRPA3P1HNRPMSSFA1HEABNSEP1NCBP2Rnu6SFRS12RNPS1SNRP70GMPCSTF1PRPF4BSNRPD3SFRS3LSM2CD2BP2SFRS9SPOPRNGTTPRPF8SSFA1HNRPH1SNRPFHNRPDDDX1U2AF1SRPK1FUSPTBP1CDC40U4 snRNAPCBP2SF3B5SNRPGHNRPUCLK4SF3B2HNRPKCSTF2TCUGBP2NUDT21SF4SFRS7SNRPBCUGBP1SFRS1RNU2WDR57HNRPCSFRS4SF3B4DHX9SRP54CSTF3U5-116KDU2AF2SF3B1HRMT1L2SFRS2FUSIP1PPM1GSMC1L1SFRS14SNRPA1SSFA1PRPF8LSM7SNRPNDDX20PRPF18SNRPERBM5SFPQSF3B3CDC40CPSF1CLK3FUSIP1HRMT1L1RNMTCPSF4FNBP3NXF1PRPF3POLR2ASNRPASUPT5HHNRPA2B1SF3A1CSTF2SNRPB2DNAJC8PHF5ASF3A3CPSF2LSM2SNRPD2SFRS16SFRS10PTBP2SNRPD1PSKH1PRPF4TXNL4AHNRPA1DICER1DHX16SNRPNSFRS6NCBP1XRN2CPSF3HNRPLSFRS8RBM17ATPHNRPABRNPC2CLK2DHX38CLK1HNRPRTMP21RBMXBRUNOL4PABPN1SRRM1DHX8SRPK2C20orf14U5 snRNAMETTL3NONODHX15


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
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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) FUSI MOUSE PMID: 11684676
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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