mRNA processing (Homo sapiens)

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13'U2 snRNPsAGsplicing factor SF3AYYYYAexon 1A5'3'Internal methylation of mRNA5'GUSerine/Argenine Rich Proteins(SR)U5pre-mRNAAdditional FactorsLariat Formation and 5'-Splice Site CleavagesnRNP Sm core complex3'U1CF IIdegradedAGCPSFSpt5Rngtt (capping enzyme)(2)Cap Binding3'3'3'YYYYCF IIAGexon 1Poly(A)-binding protein IIAdditional Factors5'Formation of the Spliceosomal E complexFormation of the active Spliceosomal C complexintron5'U2AF(3)SR-binding sitesSR protein phosphatasesU2 snRNPexon 25' G capSR-binding sites5'iPomRNA 3'-end processingUG5'AGUGCFIexon 1Note: New participating members shown at each step(2a)SR-proteinsPolr2amRNA cappingFormation of the Spliceosomal E complexheterogeneous nuclear ribonucleoproteinsSR-proteinsU4Poly(A) polymerase alpha3'Misc.A5'Putative Alternative SplicingRegulatorsAGU5 snRNPmRNA splice site selectionPrimary RNA transcript3'U2 snRNPKinases Phosphorylating RS domains?exon 2right click on blue text for detailed informationRNA helicase ACstFYYYYAexon 1Accessory Proteins5'Cleavage of mRNA at the 3'-endexon 2exon 135SR-proteinsU1 snRNP3'AAUAAACstFRegulation ofAlternative Splicingexon 2Formation of the Spliceosomal B complexYYYYPiexon 2CF IPoly(A)pb IIYYYYRNA helicaseU4/U6AGFormation of the Spliceosomal B complexFormation of the Spliceosomal A complexU6Formation of pre-mRNPsPU4:U5:U6 tri-snRNP complexsplicing factor SF3Bexon 2SR-repressor proteinsCPSFmRNA CappingCleavage at the 3'-Splice-Site and Exon LigationInternal methylation of mRNA(1)Processing of Intron-Containing Pre-mRNAU2(2c)3'P-Poly(A) polSR protein kinases3'Additional SR proteinsAdditional FactorsFormation of the Spliceosomal A complexU2AFCAFormation of pre-mRNPsSR-kinasesSR-phosphatasesFormation of the Spliceosomal C complexU1 snRNPAsnRNP Sm core complexYYYYA5'hnRNP regulatorssnRNP Sm core complexhnRNPsU6 snRNP(2b)Methylation of mRNARNAi pathwayRnmt (methyltransferase)65mRNA polyadenylationSF3b14bAAAAAAAsplicesome associated helicasesU5exon 1mRNA splicing (major pathway)5'5'U4 snRNPCPSF4NSEP1HRMT1L1SRPK1WDR57SRRM1RNU2TXNL4ASF3B4DDX1SNRPA1DHX15RNGTTRBMXPRPF4HNRPDDHX38RNMTPRPF4BSNRPD3HNRPH1PTBP1U4 snRNAFUSSNRPASF3B2NONOPCBP2NUDT21LSM2PTBP2SNRPNU2AF1U1 snRNANCBP1FUSIP1SF3A2CLK1CSTF2ATPHNRPA3P1SPOPCSTF1CLK2HNRPABU2AF2SF4SFPQRnu6CSTF2TSNRPD2DDX20RNPS1HEABSFRS8HNRPA1CDC40HNRPA2B1SFRS3RBM17CPSF3LSM7CPSF1SFRS9SRPK2SMC1L1CPSF2PAPOLANCBP2HNRPRPPM1GCLK4PSKH1FUSIP1SSFA1PABPN1RNPC2SFRS12XRN2SFRS14POLR2ASF3A1CLK3SF3B3SFRS7SFRS10PRPF4DHX16SSFA1CUGBP1PRPF3DHX9HNRPLPRPF8SNRPBC20orf14PHF5AFNBP3SNRPGSNRPB2SF3B1SF3B5SNRP70HNRPUGMPSNRPD1DHX8RBM5DICER1HNRPH2CUGBP2HNRPKSFRS1U5-116KDBRUNOL4SFRS5TMP21PRPF8NXF1SNRPEPRPF18SFRS16U5 snRNAHNRPCSNRPFSFRS4LSM2SSFA1CD2BP2DNAJC8HRMT1L2METTL3SF3A3CDC40SRP54CSTF3SNRPNHNRPMSFRS2SFRS6SUPT5H


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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44924view10:51, 6 October 2011MartijnVanIerselOntology Term : 'transcription pathway' added !
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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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