mRNA Processing (Pan troglodytes)

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AG355Rngtt (capping enzyme)Formation of pre-mRNPsiPoexon 1UGSR-proteinsexon 25U4/U6U2 snRNPs3Additional SR proteinsCF IIRNA helicase ACF IICleavage of mRNA at the 3'-endintron5Putative Alternative SplicingRegulators333SR-proteinsYYYYFormation of the Spliceosomal E complexNote: New participating members shown at each stepP-Misc.CAAAAUAAAAGmRNA capping(3)exon 2degradedAGFormation of the Spliceosomal A complexhnRNPsSR-binding sitesCap BindingRNA helicasePoly(A)pb IIsnRNP Sm core complexSR-proteinsU4:U5:U6 tri-snRNP complexSR protein kinasesSF3b14bmRNA 3'-end processingU5 snRNP65U1 snRNP3Internal methylation of mRNAexon 2PCleavage at the 3'-Splice-Site and Exon LigationPi5Poly(A) polymerase alphaU1Regulation ofAlternative Splicing3exon 2CF ImRNA splicing (major pathway)5SR-repressor proteinsCPSFpre-mRNAAAG5ALariat Formation and 5'-Splice Site Cleavage3YYYYexon 1Serine/Argenine Rich Proteins(SR)5SR-phosphatasessnRNP Sm core complexexon 1mRNA CappingAdditional Factorssplicesome associated helicasesAU2 snRNPAGRnmt (methyltransferase)heterogeneous nuclear ribonucleoproteinsU5AAAAAAASR protein phosphatases(2c)U6 snRNPYYYYYYYYMethylation of mRNAU5U2AFAGPolr2aCstFKinases Phosphorylating RS domains?Accessory Proteins(2)5Processing of Intron-Containing Pre-mRNAAsplicing factor SF3BInternal methylation of mRNAFormation of the Spliceosomal E complexAFormation of the Spliceosomal A complexFormation of the Spliceosomal B complexFormation of the Spliceosomal B complexCFI5mRNA polyadenylationexon 23Spt5snRNP Sm core complexright click on blue text for detailed information(2b)exon 1U2AF3(2a)Formation of the Spliceosomal C complexPoly(A) polPoly(A)-binding protein II5 G cap5Primary RNA transcriptmRNA splice site selectionAdditional FactorsU2 snRNPU6CPSFsplicing factor SF3ACstFU4(1)U4 snRNPYYYYRNAi pathwayYYYYFormation of the active Spliceosomal C complexexon 1SR-binding sitesU2UG33Formation of pre-mRNPsSR-kinasesexon 2GU5U1 snRNPexon 1Additional FactorshnRNP regulatorsCPSF4SNRNP70PTBP2CD2BP2EFTUD2SNRPD3HNRNPDSF3B1NCBP2CPSF2PABPN1PRPF3SF3B4METTL3FUSPRPF4DICER1CSTF1PRPF6SSFA1DHX15HNRNPRLSM2SFRS12CLK1SRPK2SFRS7SF3B3DDX1TMED10NCBP1RNU2DDX20POLR2AHNRNPA2B1SFRS3PSKH1ATPHNRNPH1SNRPD2CLK3DHX38PPM1GSNRNP40U5 snRNARBMXPRPF40ASNRPBSF3A1PTBP1CPSF1XRN2CUGBP2SMC1L1PRPF4CSTF2TCPSF3HNRNPH2DHX8HEABSNRPNHNRNPKSUPT5HHNRNPUSNRPA1CDC40SFRS14SRPK1SNRPB2SF3A2SSFA1HNRNPA1CUGBP1U2AF1SF3B5SF4PAPOLASNRPADHX16NONORHOXF2HNRNPMSNRPD1HNRNPLSFRS16SFRS5SNRPESNRPNSRRM1LSM7BRUNOL4RNMTSFPQCLK2PRMT2SF3A3SPOPSF3B2PHF5ASFRS1NSEP1SSFA1NXF1CLK4SFRS6SFRS4GMPPRPF4BSFRS9SRP54SFRS8HRMT1L2U4 snRNAHNRNPCDHX9CSTF2DNAJC8LSM2RBM5PRPF8U1 snRNAFUSIP1RNPS1FUSIP1U2AF2NUDT21CSTF3RBM39PCBP2RNGTTSNRPFTRA2BHNRPA3P1TXNL4APRPF8RBM17HNRNPABSFRS2CDC40PRPF18SNRPG


Description

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: http://en.wikipedia.org/wiki/Post-transcriptional_modification

Comments

GenMAPP notes 
Gene lists from obtained from InterPro 9-23-2003: Mm RNA-binding region RNP-1 (RNA recognition motif)
GenMAPP remarks 
Adapted from http://www.reactome.org.
HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP411(r30272) with a 78% conversion rate.

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Ontology Terms

 

Bibliography

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

History

View all...
CompareRevisionActionTimeUserComment
95768view14:20, 19 January 2018MkutmonHomology conversion update
71696view19:42, 17 October 2013MaintBotAutomated update of data sources
69321view18:44, 8 July 2013MaintBotUpdated to 2013 gpml schema
67502view11:10, 26 June 2013DdiglesOntology Term : 'spliceosome pathway' added !
48173view20:36, 9 May 2012MaintBotUpdating from human to fix xrefs
41631view02:03, 2 March 2011MaintBotRemoved redundant pathway information and comments
35271view20:26, 11 February 2010KhanspersAdded xrefs for GMP and ATP
35268view20:22, 11 February 2010KhanspersModified description
34358view22:25, 9 December 2009MaintBotAutomatic update of empty xrefs
33565view09:45, 1 December 2009MaintBotRemoved group label
31591view22:05, 13 August 2009MaintBotFixed text labels
30475view21:33, 29 July 2009MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ATPMetaboliteHMDB01532 (HMDB)
BRUNOL4GeneProduct455382 (Entrez Gene)
CD2BP2GeneProduct
CDC40GeneProduct462936 (Entrez Gene)
CLK1GeneProduct459865 (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: [email protected] 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.
CLK2GeneProduct457364 (Entrez Gene)
CLK3GeneProduct453742 (Entrez Gene)
CLK4GeneProduct471811 (Entrez Gene)
CPSF1GeneProduct
CPSF2GeneProduct738846 (Entrez Gene)
CPSF3GeneProduct459017 (Entrez Gene)
CPSF4GeneProduct463572 (Entrez Gene)
CSTF1GeneProduct
CSTF2GeneProduct473699 (Entrez Gene)
CSTF2TGeneProduct450463 (Entrez Gene)
CSTF3GeneProduct451108 (Entrez Gene)
CUGBP1GeneProduct
CUGBP2GeneProduct450298 (Entrez Gene)
DDX1GeneProduct459042 (Entrez Gene)
DDX20GeneProduct
DHX15GeneProduct461142 (Entrez Gene)
DHX16GeneProduct462546 (Entrez Gene)
DHX38GeneProduct454237 (Entrez Gene)
DHX8GeneProduct740465 (Entrez Gene)
DHX9GeneProduct457568 (Entrez Gene)
DICER1GeneProduct453137 (Entrez Gene)
DNAJC8GeneProduct469250 (Entrez Gene)
EFTUD2GeneProduct454738 (Entrez Gene)
FUSGeneProduct742385 (Entrez Gene)
FUSIP1GeneProductFUSI MOUSE PMID: 11684676
GMPMetaboliteHMDB01397 (HMDB)
HEABGeneProduct
HNRNPA1GeneProduct746119 (Entrez Gene)
HNRNPA2B1GeneProduct463299 (Entrez Gene)
HNRNPABGeneProduct462319 (Entrez Gene)
HNRNPCGeneProduct465214 (Entrez Gene)
HNRNPDGeneProduct461216 (Entrez Gene)
HNRNPH1GeneProduct462329 (Entrez Gene)
HNRNPH2GeneProduct465762 (Entrez Gene)
HNRNPKGeneProduct464554 (Entrez Gene)
HNRNPLGeneProduct456012 (Entrez Gene)
HNRNPMGeneProduct455671 (Entrez Gene)
HNRNPRGeneProduct456615 (Entrez Gene)
HNRNPUGeneProduct457867 (Entrez Gene)
HNRPA3P1GeneProduct
HRMT1L2GeneProduct
LSM2GeneProduct462569 (Entrez Gene)
LSM7GeneProduct455572 (Entrez Gene)
METTL3GeneProduct452765 (Entrez Gene)
NCBP1GeneProduct464601 (Entrez Gene)
NCBP2GeneProduct460966 (Entrez Gene)
NONOGeneProduct473661 (Entrez Gene)
NSEP1GeneProduct
NUDT21GeneProduct454100 (Entrez Gene)
NXF1GeneProduct451267 (Entrez Gene)
PABPN1GeneProduct452797 (Entrez Gene)
PAPOLAGeneProduct
PCBP2GeneProduct467006 (Entrez Gene)
PHF5AGeneProduct745456 (Entrez Gene)
POLR2AGeneProduct454463 (Entrez Gene)
PPM1GGeneProduct470340 (Entrez Gene) PMID: 12773558
PRMT2GeneProduct458620 (Entrez Gene)
PRPF18GeneProduct736885 (Entrez Gene)
PRPF3GeneProduct457272 (Entrez Gene)
PRPF40AGeneProduct459664 (Entrez Gene)
PRPF4GeneProduct464671 (Entrez Gene)
PRPF4BGeneProduct462406 (Entrez Gene)
PRPF6GeneProduct458425 (Entrez Gene)
PRPF8GeneProduct468374 (Entrez Gene)
PSKH1GeneProduct468116 (Entrez Gene) PMID: 12466556
PTBP1GeneProduct749887 (Entrez Gene)
PTBP2GeneProduct457046 (Entrez Gene)
RBM17GeneProduct450286 (Entrez Gene)
RBM39GeneProduct458443 (Entrez Gene)
RBM5GeneProduct744612 (Entrez Gene)
RBMXGeneProduct738482 (Entrez Gene)
RHOXF2GeneProduct473763 (Entrez Gene) GenBank sequence: M10329
RNGTTGeneProduct462878 (Entrez Gene)
RNMTGeneProduct455501 (Entrez Gene)
RNPS1GeneProduct750086 (Entrez Gene) PMID: 14729963
RNU2GeneProductGenBank sequence: K00027
SF3A1GeneProduct458750 (Entrez Gene)
SF3A2GeneProduct455568 (Entrez Gene)
SF3A3GeneProduct745795 (Entrez Gene)
SF3B1GeneProduct459850 (Entrez Gene)
SF3B2GeneProduct451343 (Entrez Gene)
SF3B3GeneProduct454216 (Entrez Gene)
SF3B4GeneProduct457265 (Entrez Gene)
SF3B5GeneProduct748026 (Entrez Gene)
SF4GeneProduct455874 (Entrez Gene) inferred from: SURP 2, G patch protein, UniProt:O60378
SFPQGeneProduct
SFRS12GeneProduct461839 (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.
SFRS14GeneProduct468774 (Entrez Gene)
SFRS1GeneProduct468417 (Entrez Gene) Antagonist splicing factor
SFRS16GeneProduct456120 (Entrez Gene)
SFRS2GeneProduct619467 (Entrez Gene)
SFRS3GeneProduct747921 (Entrez Gene)
SFRS4GeneProduct740597 (Entrez Gene)
SFRS5GeneProduct453000 (Entrez Gene)
SFRS6GeneProduct
SFRS7GeneProduct459167 (Entrez Gene)
SFRS8GeneProduct452374 (Entrez Gene)
SFRS9GeneProduct742440 (Entrez Gene) PMID: 12738786, PMID: 12024014 (associated with hnRNP A1 splicing)
SMC1L1GeneProduct
SNRNP40GeneProduct470976 (Entrez Gene)
SNRNP70GeneProduct747202 (Entrez Gene)
SNRPA1GeneProduct453692 (Entrez Gene)
SNRPAGeneProduct456047 (Entrez Gene)
SNRPB2GeneProduct458105 (Entrez Gene)
SNRPBGeneProduct470014 (Entrez Gene)
SNRPD1GeneProduct455329 (Entrez Gene)
SNRPD2GeneProduct456134 (Entrez Gene)
SNRPD3GeneProduct
SNRPEGeneProduct741566 (Entrez Gene)
SNRPFGeneProduct
SNRPGGeneProduct736959 (Entrez Gene)
SNRPNGeneProduct467787 (Entrez Gene)
SPOPGeneProduct455106 (Entrez Gene)
SRP54GeneProduct452858 (Entrez Gene) PMID: 14729963
SRPK1GeneProduct462640 (Entrez Gene) PMID: 12773558
SRPK2GeneProduct463641 (Entrez Gene) PMID: 12773558
SRRM1GeneProduct456632 (Entrez Gene)
SSFA1GeneProduct
SUPT5HGeneProduct456024 (Entrez Gene)
TMED10GeneProduct453045 (Entrez Gene)
TRA2BGeneProduct460905 (Entrez Gene)
TXNL4AGeneProduct
U1 snRNAGeneProductGenBank sequence: J00645
U2AF1GeneProduct737227 (Entrez Gene)
U2AF2GeneProduct
U4 snRNAGeneProductGenBank sequence: M10328, M18004
U5 snRNAGeneProductGenBank sequence: AB021173
XRN2GeneProduct458131 (Entrez Gene)

Annotated Interactions

No annotated interactions
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