mRNA Processing (Bos taurus)

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1CAsplicing factor SF3BU1 snRNPAKinases Phosphorylating RS domains?Additional SR proteinsexon 1U2 snRNPSerine/Argenine Rich Proteins(SR)Primary RNA transcript(2b)3U2AF3U6Additional FactorsCFISR-binding sitesProcessing of Intron-Containing Pre-mRNAFormation of the Spliceosomal C complexCPSF5U4(2c)AU4:U5:U6 tri-snRNP complexAdditional FactorsPU5Formation of the Spliceosomal A complexsnRNP Sm core complexexon 2Lariat Formation and 5'-Splice Site CleavageFormation of the Spliceosomal B complexmRNA 3'-end processingFormation of the Spliceosomal A complex5U4 snRNPSR-proteinsARegulation ofAlternative SplicingRngtt (capping enzyme)Formation of pre-mRNPsiPoMethylation of mRNAFormation of the active Spliceosomal C complex3CstFPutative Alternative SplicingRegulatorsPoly(A)-binding protein IIexon 1exon 2hnRNPsintronAAUAAA6555U2 snRNPSR-kinases33exon 13SR-phosphatases53CPSFU5exon 1YYYYCF II5U2AF(2a)Misc.CF IICleavage at the 3'-Splice-Site and Exon LigationUGU1degradedSR-proteinsU5 snRNPPoly(A) polymerase alphamRNA polyadenylationSF3b14bP-exon 2mRNA splice site selectionSR-binding sitesmRNA cappingFormation of the Spliceosomal E complexCap BindingRNA helicaseU4/U6YYYYYYYYU6 snRNPFormation of the Spliceosomal E complexCleavage of mRNA at the 3'-endAccessory ProteinsSpt53U2Additional FactorsAAAAAAAU1 snRNPYYYYPoly(A) polSR protein kinasesSR-repressor proteinsRNAi pathwayCF IPiexon 2pre-mRNAAGexon 1exon 2AGsnRNP Sm core complex35AG355Internal methylation of mRNA5AG5splicesome associated helicases(2)GUInternal methylation of mRNAARnmt (methyltransferase)5CstF3AGFormation of the Spliceosomal B complexYYYYPolr2aAGSR protein phosphatasesAYYYYUG3right click on blue text for detailed informationexon 2AU2 snRNPsSR-proteinsmRNA splicing (major pathway)Poly(A)pb IImRNA Cappingsplicing factor SF3AsnRNP Sm core complexFormation of pre-mRNPshnRNP regulatorsheterogeneous nuclear ribonucleoproteins(3)(1)exon 1RNA helicase ANote: New participating members shown at each step5 G capDHX15PRPF6HNRNPABCPSF4METTL3FUSIP1U5 snRNANUDT21PRPF3LSM2CLK1CPSF2SNRPNSRPK2SRSF6RBM17SUPT5HCPSF1PRPF4CLK3HNRNPH1HNRNPA2B1POLR2APRPF8NCBP1PABPN1SF3A3SRPK1RNMTSUGP2DICER1CSTF1HNRNPUGMPCD2BP2SNRPD1U1 snRNANCBP2FUSIP1SRP54LSM2PCBP2RNGTTDDX20SNRPNSF3B5DHX38SPOPCSTF2EFTUD2CSTF3LSM7FUSRnu6PTBP2SREK1U2AF2PSKH1PTBP1SRSF7HNRPA1TRA2BU2AF1SRSF5RBM39PRPF8SRSF4SNRNP40SNRPEPHF5ACLASRPCLK4SMC1ARNPS1CSTF2TPRPF4BSRRM1RBMXPRPF18ATPXRN2HNRNPMRNU2SNRPBSNRPGDHX16DHX9HRMT1L1TXNL4ASNRPFSNRPD3CDC40CPSF3TMED10SRSF9PRMT1SF3A2SNRPASRSF2DDX1SNRPB2SSFA1DNAJC8SF3A1CLP1PRPF4YBX1HNRNPRSNRPD2NXF1SSFA1HNRNPLHNRNPCHNRNPH2SFPQSUGP1CLK2CUGBP2HNRNPKSSFA1RBM5CELF1HNRPA3P1PAPOLACDC40SRSF1PRPF40ASF3B4SNRNP70SNRPA1HNRNPDSF3B1NONOCELF4SFSWAPU4 snRNADHX8SF3B2SRSF3PPM1GSF3B3


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


This pathway was inferred from Homo sapiens pathway WP411(r45374) with a 90% conversion rate.

Quality Tags

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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95764view14:18, 19 January 2018MkutmonHomology conversion update
80888view15:29, 30 June 2015Mkutmonhomology conversion
71421view19:02, 17 October 2013MaintBotAutomated update of data sources
67492view11:08, 26 June 2013DdiglesOntology Term : 'spliceosome pathway' added !
63389view00:03, 10 May 2013MaintBotUpdated to 2013 gpml schema
48124view05:41, 9 May 2012KhanspersUpdating from human to fix xref duplication
40562view19:32, 1 March 2011MaintBotRemoved redundant pathway information and comments
35238view19:44, 11 February 2010Khanspersupdated xrefs
35235view19:37, 11 February 2010KhanspersModified description
33800view00:16, 9 December 2009MaintBotAutomatic update of empty xrefs
32497view12:47, 17 August 2009MaintBotFixed text labels
32189view12:34, 15 August 2009MaintBotFixed text labels
31663view11:39, 14 August 2009MaintBotFixed group labels
31195view19:31, 13 August 2009MaintBotFixed text labels
30592view22:13, 29 July 2009MaintBotNew pathway

External references


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NameTypeDatabase referenceComment
ATPMetabolite1927-31-7 (CAS)
CD2BP2GeneProduct513857 (Entrez Gene)
CDC40GeneProduct514003 (Entrez Gene)
CELF1GeneProduct540475 (Entrez Gene)
CELF4GeneProduct535177 (Entrez Gene)
CLASRPGeneProduct509208 (Entrez Gene)
CLK1GeneProductPMID: 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.
CLK2GeneProduct512737 (Entrez Gene)
CLK3GeneProduct505499 (Entrez Gene)
CLK4GeneProduct529633 (Entrez Gene)
CLP1GeneProduct506507 (Entrez Gene)
CPSF1GeneProduct282703 (Entrez Gene)
CPSF2GeneProduct327689 (Entrez Gene)
CPSF3GeneProduct281712 (Entrez Gene)
CPSF4GeneProduct280875 (Entrez Gene)
CSTF1GeneProduct507051 (Entrez Gene)
CSTF2GeneProduct282588 (Entrez Gene)
CSTF2TGeneProduct783569 (Entrez Gene)
CSTF3GeneProduct508491 (Entrez Gene)
DDX1GeneProduct510816 (Entrez Gene)
DDX20GeneProduct528433 (Entrez Gene)
DHX15GeneProduct512327 (Entrez Gene)
DHX16GeneProduct506405 (Entrez Gene)
DHX38GeneProduct520046 (Entrez Gene)
DHX8GeneProduct536093 (Entrez Gene)
DHX9GeneProduct281115 (Entrez Gene)
DICER1GeneProduct337871 (Entrez Gene)
DNAJC8GeneProduct614259 (Entrez Gene)
EFTUD2GeneProduct509425 (Entrez Gene)
FUSGeneProduct280796 (Entrez Gene)
FUSIP1GeneProductFUSI MOUSE PMID: 11684676
GMPMetabolite85-32-5 (CAS)
HNRNPA2B1GeneProduct507564 (Entrez Gene)
HNRNPABGeneProduct513410 (Entrez Gene)
HNRNPCGeneProduct510852 (Entrez Gene)
HNRNPDGeneProduct527471 (Entrez Gene)
HNRNPH1GeneProduct541202 (Entrez Gene)
HNRNPH2GeneProduct534001 (Entrez Gene)
HNRNPKGeneProduct528135 (Entrez Gene)
HNRNPLGeneProduct504520 (Entrez Gene)
HNRNPMGeneProduct515290 (Entrez Gene)
HNRNPRGeneProduct512479 (Entrez Gene)
HNRNPUGeneProduct539950 (Entrez Gene)
LSM2GeneProduct538662 (Entrez Gene)
LSM7GeneProduct509920 (Entrez Gene)
METTL3GeneProduct540339 (Entrez Gene)
NCBP1GeneProduct100124428 (Entrez Gene)
NCBP2GeneProduct510872 (Entrez Gene)
NONOGeneProduct615175 (Entrez Gene)
NUDT21GeneProduct518859 (Entrez Gene)
NXF1GeneProduct512136 (Entrez Gene)
PABPN1GeneProduct282298 (Entrez Gene)
PAPOLAGeneProduct338051 (Entrez Gene)
PCBP2GeneProduct540653 (Entrez Gene)
PHF5AGeneProduct507180 (Entrez Gene)
POLR2AGeneProduct282312 (Entrez Gene)
PPM1GGeneProduct286880 (Entrez Gene) PMID: 12773558
PRMT1GeneProduct520388 (Entrez Gene)
PRPF18GeneProduct507639 (Entrez Gene)
PRPF3GeneProduct510322 (Entrez Gene)
PRPF40AGeneProduct100301114 (Entrez Gene)
PRPF4GeneProduct508735 (Entrez Gene)
PRPF4BGeneProduct512236 (Entrez Gene)
PRPF6GeneProduct534228 (Entrez Gene)
PRPF8GeneProduct507371 (Entrez Gene)
PSKH1GeneProduct509656 (Entrez Gene) PMID: 12466556
PTBP1GeneProduct282018 (Entrez Gene)
RBM17GeneProduct512694 (Entrez Gene)
RBM39GeneProduct508722 (Entrez Gene)
RBM5GeneProduct534216 (Entrez Gene)
RBMXGeneProduct509591 (Entrez Gene)
RNGTTGeneProduct511408 (Entrez Gene)
RNMTGeneProduct511555 (Entrez Gene)
RNPS1GeneProduct504506 (Entrez Gene) PMID: 14729963
RNU2GeneProductGenBank sequence: K00027
Rnu6RnaGenBank sequence: M10329
SF3A1GeneProduct504381 (Entrez Gene)
SF3A2GeneProduct789082 (Entrez Gene)
SF3A3GeneProduct523250 (Entrez Gene)
SF3B1GeneProduct510177 (Entrez Gene)
SF3B2GeneProduct531931 (Entrez Gene)
SF3B3GeneProduct504962 (Entrez Gene)
SF3B4GeneProduct506123 (Entrez Gene)
SF3B5GeneProduct574400 (Entrez Gene)
SFPQGeneProduct618226 (Entrez Gene)
SFSWAPGeneProduct512326 (Entrez Gene)
SMC1AGeneProduct282370 (Entrez Gene)
SNRNP40GeneProduct534645 (Entrez Gene)
SNRNP70GeneProduct535113 (Entrez Gene)
SNRPA1GeneProduct512584 (Entrez Gene)
SNRPAGeneProduct509802 (Entrez Gene)
SNRPB2GeneProduct767873 (Entrez Gene)
SNRPBGeneProduct613304 (Entrez Gene)
SNRPD1GeneProduct508788 (Entrez Gene)
SNRPD2GeneProduct514932 (Entrez Gene)
SNRPD3GeneProduct617823 (Entrez Gene)
SNRPEGeneProduct531493 (Entrez Gene)
SNRPGGeneProduct522621 (Entrez Gene)
SNRPNGeneProduct780877 (Entrez Gene)
SPOPGeneProduct530618 (Entrez Gene)
SREK1GeneProduct507801 (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.
SRP54GeneProduct614017 (Entrez Gene) PMID: 14729963
SRPK1GeneProduct512631 (Entrez Gene) PMID: 12773558
SRPK2GeneProduct505945 (Entrez Gene) PMID: 12773558
SRRM1GeneProduct784123 (Entrez Gene)
SRSF1GeneProduct615796 (Entrez Gene) Antagonist splicing factor
SRSF2GeneProduct508312 (Entrez Gene)
SRSF3GeneProduct540276 (Entrez Gene)
SRSF4GeneProduct614310 (Entrez Gene)
SRSF5GeneProduct510474 (Entrez Gene)
SRSF6GeneProduct507828 (Entrez Gene)
SRSF7GeneProduct507066 (Entrez Gene)
SRSF9GeneProduct509905 (Entrez Gene) PMID: 12738786, PMID: 12024014 (associated with hnRNP A1 splicing)
SUGP1GeneProduct533971 (Entrez Gene) inferred from: SURP 2, G patch protein, UniProt:O60378
SUGP2GeneProduct516567 (Entrez Gene)
SUPT5HGeneProduct519808 (Entrez Gene)
TMED10GeneProduct529761 (Entrez Gene)
TRA2BGeneProduct615156 (Entrez Gene)
TXNL4AGeneProduct535457 (Entrez Gene)
U1 snRNARnaGenBank sequence: J00645
U2AF1GeneProduct512680 (Entrez Gene)
U2AF2GeneProduct507895 (Entrez Gene)
U4 snRNARnaGenBank sequence: M10328, M18004
U5 snRNARnaGenBank sequence: AB021173
XRN2GeneProduct517417 (Entrez Gene)
YBX1GeneProduct287023 (Entrez Gene)

Annotated Interactions

No annotated interactions
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