mRNA processing (Danio rerio)

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snRNP Sm core complexU4:U5:U6 tri-snRNP complexCPSFAGPoly(A) polRNAi pathwayInternal methylation of mRNA3exon 1RNA helicase A5PU2 snRNPRegulation ofSR-proteinsSR protein phosphatasesmRNA 3’-end processingexon 2SR-repressor proteinsmRNA splicing (major pathway)SR-binding sitesmRNA splice site selectionMisc.ARegulatorsFormation of pre-mRNPsGU(3)YYYY(1)U2 snRNPYYYYAdditional FactorsAGexon 15SR-binding sitesSR-proteins3Formation of the Spliceosomal A complexright click on blue text for detailed informationU2 snRNPsRngtt (capping enzyme)3AHOMOLOGY MAPP35Rnmt (methyltransferase)ATPFormation of the Spliceosomal E complexSF3b14bU1CF IIAAAAAAA3U5 snRNPmRNA CappingSerine/Argenine Rich Proteins(SR)Pi(2c)U4 snRNPCstFCleavage at the 3’-Splice-Site and Exon LigationFormation of the Spliceosomal B complexSR-proteinshnRNPsPrimary RNA transcriptFormation of the Spliceosomal A complexexon 2exon 1mRNA cappingSR-kinasesAUGPoly(A)pb IIU2AF35Processing of Intron-Containing Pre-mRNAexon 1GMP5snRNP Sm core complexU2AFexon 2Poly(A) polymerase alpha3Note: New participating members shown at each step353degradedexon 2CstFFormation of the active Spliceosomal C complexexon 2Additional SR proteinssplicing factor SF3AU5Alternative SplicingFormation of the Spliceosomal E complexAAUAAAAdditional FactorsP-YYYY(2a)5heterogeneous nuclear ribonucleoproteinsYYYY3AG(2)intronSR-phosphatasessnRNP Sm core complexSpt5A5U2Accessory Proteinsexon 25 G cap5(2b)exon 1U4/U6RNA helicaseCFIPutative Alternative SplicingAGCleavage of mRNA at the 3’-endSR protein kinasesCF IIAFormation of pre-mRNPsMethylation of mRNA5Cap BindingAGYYYYU1 snRNPUGCPSFU4Internal methylation of mRNACAsplicing factor SF3BYYYYiPoPoly(A)-binding protein IIFormation of the Spliceosomal C complexpre-mRNAU6 snRNPCF I3Lariat Formation and 5’-Splice Site CleavageU5exon 1U1 snRNP5U6AhnRNP regulatorsKinases Phosphorylating RS domains?AGsplicesome associated helicasesAdditional Factors5653Polr2amRNA polyadenylationFormation of the Spliceosomal B complexprpf18zgc:85681zgc:92484cpsf5supt5hSRPK2srpk1SFRS4U4 snRNACSTF2Tzgc:86860prpf4SSFA1CLK1spopzgc:100974U5 snRNAFNBP3hnrpa1u2af1hnrpunarDHX38zgc:110732HNRPH2zgc:55623snrp70PRPF3zgc:55876SF4DICER1HRMT1L1SF3B1zgc:85960snrpflcd2bp2RNMTSNRPB2HNRPA2B1HEABzgc:85979zgc:109706SFRS5sf3b5cstf3SFRS14DHX9zgc:77804RBM5SNRPNBRUNOL4zgc:77560EFTUD2zgc:55440phf5acugbp2sfrs3HNRPA3SMC1L1HNRPDDDX20FUSIP1zgc:55429hnrpabhrmt1l2srp54DHX15PTBP2U1 snRNAzgc:56390CLK3HNRPRzgc:103688PRPF8sfrs10c20orf14LSM7HNRPCSF3B2SNRPBSFRS6NCBP1SSFA1CSTF2PRPF8ppm1gsnrparngttDHX8SNRPD3zgc:86860SNRPNCLK4POLR2Asf3b4zgc:103632zgc:77093sf3a2SSFA1sf3a1prpf4hnrpkDNAJC8SFPQzgc:77155zgc:101832FUSIP1zgc:77449cpsf3CPSF1zgc:56184snrpd1sfrs1SFRS16zgc:110689nonoxrn2srrm1RBMXsmx5SF3A3dhx16wdr57rnpc2smx5DDX1PSKH1nsep1cugbp1NXF1zgc:56682CLK2ncbp2rbm17Rnu6RNPS1HNRPMpcbp2RNU2


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.

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History

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CompareRevisionActionTimeUserComment
122797view02:12, 18 May 2022AlexanderPicocleaning up broken comments
91976view14:37, 10 April 2017LWackersUpdated human annotations to zebrafish orthologues.
91952view13:04, 6 April 2017LWackersUpdated annotations and added missing ones.
71979view00:30, 24 October 2013MaintBotremoved data source from nodes without identifier
69959view20:55, 11 July 2013MaintBotupdated to 2013 schema
67499view11:09, 26 June 2013DdiglesOntology Term : 'spliceosome pathway' added !
40828view22:18, 1 March 2011MaintBotRemoved redundant pathway information and comments
35245view19:53, 11 February 2010KhanspersModified description
34214view21:32, 9 December 2009MaintBotAutomatic update of empty xrefs
21662view11:32, 14 November 2008MaintBot[[Pathway:Danio rerio:mRNA processing Reactome]] moved to [[Pathway:WP467]]: Moved to stable identifier
12032view08:44, 15 May 2008MaintBotAdded to category $category
12030view08:44, 15 May 2008NsalomonisUploaded new pathway

External references

DataNodes

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NameTypeDatabase referenceComment
BRUNOL4GeneProduct
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: [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.
CLK2GeneProduct
CLK3GeneProduct
CLK4GeneProduct
CPSF1GeneProduct432372 (Entrez Gene)
CSTF2GeneProduct386806 (Entrez Gene)
CSTF2TGeneProduct
DDX1GeneProduct
DDX20GeneProduct556273 (Entrez Gene)
DHX15GeneProduct321931 (Entrez Gene)
DHX38GeneProduct393850 (Entrez Gene)
DHX8GeneProduct
DHX9GeneProduct
DICER1GeneProduct324724 (Entrez Gene)
DNAJC8GeneProduct321414 (Entrez Gene)
EFTUD2GeneProduct393480 (Entrez Gene)
FNBP3GeneProduct
FUSIP1GeneProductFUSI_MOUSE PMID: 11684676
HEABGeneProduct
HNRPA2B1GeneProduct
HNRPA3GeneProduct
HNRPCGeneProduct
HNRPDGeneProduct
HNRPH2GeneProduct
HNRPMGeneProduct
HNRPRGeneProduct406735 (Entrez Gene)
HRMT1L1GeneProduct
LSM7GeneProduct573047 (Entrez Gene)
NCBP1GeneProduct
NXF1GeneProduct323865 (Entrez Gene)
POLR2AGeneProduct553347 (Entrez Gene)
PRPF3GeneProduct403072 (Entrez Gene)
PRPF8GeneProduct393951 (Entrez Gene)
PSKH1GeneProduct554840 (Entrez Gene) PMID: 12466556
PTBP2GeneProduct
RBM5GeneProduct324302 (Entrez Gene)
RBMXGeneProduct321860 (Entrez Gene)
RNMTGeneProduct
RNPS1GeneProduct327020 (Entrez Gene) PMID: 14729963
RNU2GeneProductGenBank sequence: K00027
Rnu6GeneProductGenBank sequence: M10329
SF3A3GeneProduct446168 (Entrez Gene)
SF3B1GeneProduct446117 (Entrez Gene)
SF3B2GeneProduct
SF4GeneProductinferred from: SURP 2, G patch protein, UniProt:O60378
SFPQGeneProduct406564 (Entrez Gene)
SFRS14GeneProduct
SFRS16GeneProduct
SFRS4GeneProduct321872 (Entrez Gene)
SFRS5GeneProduct
SFRS6GeneProduct
SMC1L1GeneProduct
SNRPB2GeneProduct402896 (Entrez Gene)
SNRPBGeneProduct402966 (Entrez Gene)
SNRPD3GeneProduct415171 (Entrez Gene)
SNRPNGeneProduct
SRPK2GeneProductPMID: 12773558
SSFA1GeneProduct
U1 snRNAGeneProductGenBank sequence: J00645
U4 snRNAGeneProductGenBank sequence: M10328, M18004
U5 snRNAGeneProductGenBank sequence: AB021173
c20orf14GeneProduct323855 (Entrez Gene)
cd2bp2GeneProduct393936 (Entrez Gene)
cpsf3GeneProduct324554 (Entrez Gene)
cpsf5GeneProduct394092 (Entrez Gene)
cstf3GeneProduct406326 (Entrez Gene)
cugbp1GeneProduct58137 (Entrez Gene)
cugbp2GeneProduct373117 (Entrez Gene)
dhx16GeneProduct336645 (Entrez Gene)
hnrpa1GeneProduct378453 (Entrez Gene)
hnrpabGeneProduct321466 (Entrez Gene)
hnrpkGeneProduct406267 (Entrez Gene)
hnrpuGeneProduct334490 (Entrez Gene)
hrmt1l2GeneProduct321974 (Entrez Gene)
narGeneProduct30203 (Entrez Gene)
ncbp2GeneProduct192325 (Entrez Gene)
nonoGeneProduct321994 (Entrez Gene)
nsep1GeneProduct58144 (Entrez Gene)
pcbp2GeneProduct321844 (Entrez Gene)
phf5aGeneProduct286774 (Entrez Gene)
ppm1gGeneProduct368275 (Entrez Gene) PMID: 12773558
prpf18GeneProduct431751 (Entrez Gene)
prpf4GeneProduct326944 (Entrez Gene)
rbm17GeneProduct393889 (Entrez Gene)
rngttGeneProduct405803 (Entrez Gene)
rnpc2GeneProduct406251 (Entrez Gene)
sf3a1GeneProduct368732 (Entrez Gene)
sf3a2GeneProduct394018 (Entrez Gene)
sf3b4GeneProduct192318 (Entrez Gene)
sf3b5GeneProduct436751 (Entrez Gene)
sfrs10GeneProduct394172 (Entrez Gene)
sfrs1GeneProduct393565 (Entrez Gene) Antagonist splicing factor
sfrs3GeneProduct368925 (Entrez Gene)
smx5GeneProduct57924 (Entrez Gene)
snrp70GeneProduct445398 (Entrez Gene)
snrpaGeneProduct324121 (Entrez Gene)
snrpd1GeneProduct192331 (Entrez Gene)
snrpflGeneProduct445404 (Entrez Gene)
spopGeneProduct394105 (Entrez Gene)
srp54GeneProduct393963 (Entrez Gene) PMID: 14729963
srpk1GeneProduct323679 (Entrez Gene) PMID: 12773558
srrm1GeneProduct406751 (Entrez Gene)
supt5hGeneProduct64275 (Entrez Gene)
u2af1GeneProduct192328 (Entrez Gene)
wdr57GeneProduct393292 (Entrez Gene)
xrn2GeneProduct321940 (Entrez Gene)
zgc:100974GeneProduct445219 (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.
zgc:101832GeneProduct492511 (Entrez Gene)
zgc:103632GeneProduct449780 (Entrez Gene)
zgc:103688GeneProduct447922 (Entrez Gene)
zgc:109706GeneProduct404041 (Entrez Gene)
zgc:110689GeneProduct323490 (Entrez Gene)
zgc:110732GeneProduct550244 (Entrez Gene)
zgc:55429GeneProduct394074 (Entrez Gene)
zgc:55440GeneProduct406824 (Entrez Gene)
zgc:55623GeneProduct406758 (Entrez Gene)
zgc:55876GeneProduct323700 (Entrez Gene)
zgc:56184GeneProduct394143 (Entrez Gene)
zgc:56390GeneProduct394058 (Entrez Gene)
zgc:56682GeneProduct393979 (Entrez Gene)
zgc:77093GeneProduct337552 (Entrez Gene)
zgc:77155GeneProduct402972 (Entrez Gene)
zgc:77449GeneProduct405835 (Entrez Gene) PMID: 12738786, PMID: 12024014 (associated with hnRNP A1 splicing)
zgc:77560GeneProduct324238 (Entrez Gene)
zgc:77804GeneProduct402989 (Entrez Gene)
zgc:85681GeneProduct326716 (Entrez Gene)
zgc:85960GeneProduct321556 (Entrez Gene)
zgc:85979GeneProduct406543 (Entrez Gene)
zgc:86860GeneProduct494534 (Entrez Gene)
zgc:92484GeneProduct436657 (Entrez Gene)

Annotated Interactions

No annotated interactions
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