mRNA Processing (Pan troglodytes)

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1RNA helicase(2b)CFIheterogeneous nuclear ribonucleoproteinsU2 snRNPsAAUAAAexon 1AGUAccessory ProteinsSpt5Additional SR proteinsAGYYYYFormation of pre-mRNPsU4:U5:U6 tri-snRNP complexexon 2snRNP Sm core complexAAAAAAA(2)SR-phosphatasesright click on blue text for detailed informationCstFU2 snRNPSR-proteinspre-mRNA3CF IU1SR protein phosphatasesmRNA 3'-end processingsnRNP Sm core complex(1)mRNA CappingRnmt (methyltransferase)exon 1AGAPolr2asplicing factor SF3B5snRNP Sm core complexAGFormation of the Spliceosomal E complex5exon 15mRNA splice site selectionFormation of pre-mRNPs3U4/U6CPSF335CAYYYYU5exon 1Regulation ofAlternative Splicing3Formation of the Spliceosomal B complex3SR-proteins5exon 2Additional Factors(3)Internal methylation of mRNAU1 snRNPPoly(A) polInternal methylation of mRNASR protein kinasesUGFormation of the Spliceosomal B complexU1 snRNP55Formation of the Spliceosomal C complex5exon 2U4 snRNPPoly(A)-binding protein IIFormation of the Spliceosomal A complexmRNA polyadenylationSR-binding sitesPASR-repressor proteinsexon 23Cleavage of mRNA at the 3'-endU2YYYYPutative Alternative SplicingRegulatorsU6splicesome associated helicasesCap BindingYYYY5Serine/Argenine Rich Proteins(SR)iPoU6 snRNP3Processing of Intron-Containing Pre-mRNARNA helicase AKinases Phosphorylating RS domains?AGNote: New participating members shown at each stepFormation of the Spliceosomal E complexSR-kinases5SF3b14bhnRNP regulatorsmRNA splicing (major pathway)Formation of the active Spliceosomal C complexSR-proteinsdegradedAG3exon 2U2AFCPSFUGU5Rngtt (capping enzyme)hnRNPsCF IIMisc.5 G capU5 snRNPFormation of the Spliceosomal A complexU2 snRNPAAGPrimary RNA transcriptP-3U2AFSR-binding sites5Additional FactorsMethylation of mRNAPisplicing factor SF3APoly(A) polymerase alphaA(2c)Cleavage at the 3'-Splice-Site and Exon LigationYYYYmRNA cappingexon 1(2a)CstFintronLariat Formation and 5'-Splice Site CleavageA5exon 23exon 165Poly(A)pb IIRNAi pathwayAdditional FactorsU4YYYYCF II3SRSF3METTL3DHX38DHX15CPSF4SNRPFEFTUD2SF3B1DNAJC8CSTF1TRA2BRBM5PCBP2PABPN1SNRPD1PRPF40AHEABRBMXRNU2CLK1PRPF3SRSF1SFPQSSFA1FUSIP1DDX20SF3B3SNRPNU2AF1PRPF6CLK2SPOPSMC1L1PHF5ASNRNP40LOC451173FUSIP1SRSF6SNRPEDHX16HNRNPLDHX9SRPK2SNRPD2HNRNPH1HNRNPKSRSF4LSM7SUGP2SREK1HNRNPDCELF2LSM2SNRPA1ATPPTBP1PRPF4PRPF18LSM2CPSF1GMPU1 snRNACDC40SNRPD3SF3B4HNRNPUSUPT5HHNRNPMPRPF8SRSF5SNRPGSF3A1SNRPACELF4HNRNPH2CLK4PSKH1RBM17SUGP1NCBP2SFSWAPHNRNPABCSTF3U4 snRNAXRN2SNRPNDDX1NONORNGTTSRRM1HNRPA3P1PTBP2LOC470311CLASRPSRPK1TXNL4ASRSF2PRPF4CSTF2TRNPS1NUDT21HRMT1L2SNRPB2POLR2AHNRNPRSF3A2LOC467947SSFA1RBM39RNMTNXF1DHX8HNRNPA2B1SSFA1SF3B5PRMT2PAPOLALOC746119CDC40SNRNP70SF3A3PRPF4BCLK3TMED10U2AF2CPSF3NCBP1SRSF9SRSF7DICER1HNRNPCPRPF8Rnu6PPM1GFUSSF3B2U5 snRNACPSF2CSTF2SNRPBSRP54


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

Pathway adapted from http://www.reactome.org.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP411(r45374) with a 86% 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
ATPMetabolite1927-31-7 (CAS)
CDC40GeneProduct462936 (Entrez Gene)
CELF2GeneProduct450298 (Entrez Gene)
CELF4GeneProduct455382 (Entrez Gene)
CLASRPGeneProduct456120 (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)
CSTF1GeneProduct100610308 (Entrez Gene)
CSTF2GeneProduct473699 (Entrez Gene)
CSTF2TGeneProduct450463 (Entrez Gene)
CSTF3GeneProduct451108 (Entrez Gene)
DDX1GeneProduct459042 (Entrez Gene)
DDX20GeneProduct457107 (Entrez Gene)
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
GMPMetabolite85-32-5 (CAS)
HEABGeneProduct
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
LOC451173GeneProduct451173 (Entrez Gene)
LOC467947GeneProduct467947 (Entrez Gene)
LOC470311GeneProduct470311 (Entrez Gene)
LOC746119GeneProduct746119 (Entrez Gene)
LSM2GeneProduct462569 (Entrez Gene)
LSM7GeneProduct455572 (Entrez Gene)
METTL3GeneProduct452765 (Entrez Gene)
NCBP1GeneProduct464601 (Entrez Gene)
NCBP2GeneProduct460966 (Entrez Gene)
NONOGeneProduct473661 (Entrez Gene)
NUDT21GeneProduct454100 (Entrez Gene)
NXF1GeneProduct451267 (Entrez Gene)
PABPN1GeneProduct452797 (Entrez Gene)
PAPOLAGeneProduct100614622 (Entrez Gene)
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)
RNGTTGeneProduct462878 (Entrez Gene)
RNMTGeneProduct455501 (Entrez Gene)
RNPS1GeneProduct750086 (Entrez Gene) PMID: 14729963
RNU2GeneProductGenBank sequence: K00027
Rnu6RnaGenBank sequence: M10329
SF3A1GeneProduct458750 (Entrez Gene)
SF3A2GeneProduct455568 (Entrez Gene)
SF3A3GeneProduct745795 (Entrez Gene)
SF3B1GeneProduct459850 (Entrez Gene)
SF3B2GeneProduct451343 (Entrez Gene)
SF3B3GeneProduct454216 (Entrez Gene)
SF3B4GeneProduct457265 (Entrez Gene)
SF3B5GeneProduct748026 (Entrez Gene)
SFPQGeneProduct
SFSWAPGeneProduct452374 (Entrez Gene)
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)
SNRPNGeneProduct
SPOPGeneProduct455106 (Entrez Gene)
SREK1GeneProduct461839 (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.
SRP54GeneProduct452858 (Entrez Gene) PMID: 14729963
SRPK1GeneProduct462640 (Entrez Gene) PMID: 12773558
SRPK2GeneProduct463641 (Entrez Gene) PMID: 12773558
SRRM1GeneProduct456632 (Entrez Gene)
SRSF1GeneProduct468417 (Entrez Gene) Antagonist splicing factor
SRSF2GeneProduct619467 (Entrez Gene)
SRSF3GeneProduct747921 (Entrez Gene)
SRSF4GeneProduct740597 (Entrez Gene)
SRSF5GeneProduct453000 (Entrez Gene)
SRSF6GeneProduct469946 (Entrez Gene)
SRSF7GeneProduct459167 (Entrez Gene)
SRSF9GeneProduct742440 (Entrez Gene) PMID: 12738786, PMID: 12024014 (associated with hnRNP A1 splicing)
SSFA1GeneProduct
SUGP1GeneProduct455874 (Entrez Gene) inferred from: SURP 2, G patch protein, UniProt:O60378
SUGP2GeneProduct468774 (Entrez Gene)
SUPT5HGeneProduct456024 (Entrez Gene)
TMED10GeneProduct453045 (Entrez Gene)
TRA2BGeneProduct460905 (Entrez Gene)
TXNL4AGeneProduct
U1 snRNARnaGenBank sequence: J00645
U2AF1GeneProduct737227 (Entrez Gene)
U2AF2GeneProduct
U4 snRNARnaGenBank sequence: M10328, M18004
U5 snRNARnaGenBank sequence: AB021173
XRN2GeneProduct458131 (Entrez Gene)

Annotated Interactions

No annotated interactions
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