mRNA processing (Danio rerio)

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A3SR protein kinasesGUexon 2Aexon 1CAU4/U6CstFsplicing factor SF3BSR-phosphatasesSR-binding sitesCstFSR-kinasesGMPSR-proteins3AGAU25Formation of the active Spliceosomal C complexRngtt (capping enzyme)5splicing factor SF3APoly(A)pb IIU5U2AFexon 2(2b)Kinases Phosphorylating RS domains?Putative Alternative SplicingYYYYAAUAAA5 G capright click on blue text for detailed informationFormation of the Spliceosomal B complexSR-repressor proteins3U1 snRNPATP533Formation of the Spliceosomal E complexSF3b14bMethylation of mRNA5Additional SR proteinsRNA helicasesplicesome associated helicasesSR protein phosphatases3Polr2aLariat Formation and 5'-Splice Site CleavageU2 snRNPsexon 2U2 snRNPexon 2pre-mRNAAdditional Factorsexon 1snRNP Sm core complexCF IUGCF IISpt5Processing of Intron-Containing Pre-mRNAAdditional FactorsCleavage of mRNA at the 3'-endsnRNP Sm core complexAGexon 1Poly(A) polRNA helicase AU6 snRNPYYYYRnmt (methyltransferase)HOMOLOGY MAPPRNAi pathwayCap BindingFormation of pre-mRNPsAlternative Splicingexon 2Regulation ofAGMisc.Poly(A) polymerase alphaFormation of the Spliceosomal B complexNote: New participating members shown at each stepmRNA cappingiPomRNA splicing (major pathway)535U5CPSFAccessory ProteinsRegulatorsYYYYmRNA splice site selection3YYYYU4 snRNPAAG5(2c)5degradedexon 1SR-proteinsexon 2Aexon 1Formation of the Spliceosomal A complex(2a)CFI35(3)AU5 snRNPP-CF IIInternal methylation of mRNAFormation of the Spliceosomal A complexYYYYU2 snRNPPUGPiFormation of the Spliceosomal C complexU1 snRNPU2AFU4:U5:U6 tri-snRNP complexAAAAAAAYYYY3mRNA CappingPrimary RNA transcriptintronU13AGsnRNP Sm core complexFormation of pre-mRNPsheterogeneous nuclear ribonucleoproteins3CPSF5655U6Additional Factors(1)mRNA 3'-end processingSerine/Argenine Rich Proteins(SR)SR-proteinsCleavage at the 3'-Splice-Site and Exon LigationInternal methylation of mRNAAG5hnRNP regulatorshnRNPsexon 1mRNA polyadenylation(2)Poly(A)-binding protein IIU4SR-binding sitesFormation of the Spliceosomal E complexhnrnpdsmx5hnrpabhnrnph1lCLK3srp54ptbp1asfrs10clk2ac20orf14U1 snRNASF3A3DNAJC8SFRS4rbm17u2af1spophnrnpkprpf3U4 snRNAwdr57phf5aNCBP1sf3a2snrpbhnrnpmcdc40prpf18cpsf2ssfa1snrpasf3b4Rnu6hnrnpa3sfrs16clk4addx1ptbp2asnrpb2sugp1ybx1EFTUD2sfrs1snrpflnxf1SNRPBprpf4bbHNRPH2PRPF8SRPK2POLR2Apcbp2RNU2sfpqfussf3a1snrpbdhx16hnrnprhnrpa1HNRPA2B1U5 snRNAdicer1CLK1srrm1snrpgprpf40aHEABzgc:55440smc1alcstf3rbm5cugbp2prpf4snrpd1prpf4ppm1glsm7ddx20mettl3sfrs3sfrs6aRBMXDHX9SFRS14dhx8cd2bp2sfrs5aDHX38ncbp2PRPF8cugbp1sfswapsnrpd2cstf1papolacpsf5prmt1srek1rnps1txnl4aPSKH1prmt2sf3b5cpsf3tmed10supt5hsf3b2sf3b1nonossfa1srsf7asnrpedhx15snrpa1hnrplCSTF2Tsrsf2bsrsf10aRNMTcelf4xrn2ssfa1pabn1srpk1cstf2rnpc2hnrnpccpsf1zgc:77804SNRPD3narhnrpurngttsmx5srsf9snrp70clk2bclk4bptbp2bsrsf10bsrsf10asrsf10bsfrs5bsfrs6b


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:


GenMAPP notes 
Gene lists from obtained from InterPro 9-23-2003: Mm_RNA-binding region RNP-1 (RNA recognition motif)
GenMAPP remarks 
Adapted from

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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


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NameTypeDatabase referenceComment
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.
DHX38GeneProduct393850 (Entrez Gene)
DHX9GeneProductENSDARG00000079725 (Ensembl)
DNAJC8GeneProductENSDARG00000059373 (Ensembl)
EFTUD2GeneProduct393480 (Entrez Gene)
HEABGeneProductENSDARG00000063663 (Ensembl)
NCBP1GeneProduct101885456 (Entrez Gene)
POLR2AGeneProduct553347 (Entrez Gene)
PRPF8GeneProduct393951 (Entrez Gene)
PSKH1GeneProduct554840 (Entrez Gene) PMID: 12466556
RBMXGeneProduct321860 (Entrez Gene)
RNMTGeneProductENSDARG00000070553 (Ensembl)
RNU2GeneProductGenBank sequence: K00027
Rnu6GeneProductGenBank sequence: M10329
SF3A3GeneProduct446168 (Entrez Gene)
SFRS14GeneProductNo zebrafish ortholog for this gene on NCBI, maybe remove?
SFRS4GeneProduct321872 (Entrez Gene)
SNRPBGeneProduct402966 (Entrez Gene)
SNRPD3GeneProduct415171 (Entrez Gene)
SRPK2GeneProduct100333293 (Entrez Gene) PMID: 12773558
U1 snRNAGeneProductGenBank sequence: J00645
U4 snRNAGeneProductGenBank sequence: M10328, M18004
U5 snRNAGeneProductGenBank sequence: AB021173
c20orf14GeneProduct323855 (Entrez Gene)
cd2bp2GeneProduct393936 (Entrez Gene)
cdc40GeneProduct494534 (Entrez Gene)
celf4GeneProductENSDARG00000070045 (Ensembl) Alias for BRUNOL4
clk2aGeneProductENSDARG00000062954 (Ensembl)
clk2bGeneProductENSDARG00000059870 (Ensembl)
clk4aGeneProductENSDARG00000089372 (Ensembl)
clk4bGeneProductENSDARG00000005908 (Ensembl)
cpsf1GeneProduct432372 (Entrez Gene)
cpsf2GeneProduct436657 (Entrez Gene)
cpsf3GeneProduct324554 (Entrez Gene)
cpsf5GeneProduct394092 (Entrez Gene)
cstf1GeneProduct324238 (Entrez Gene)
cstf2GeneProduct386806 (Entrez Gene)
cstf3GeneProduct406326 (Entrez Gene)
cugbp1GeneProduct58137 (Entrez Gene)
cugbp2GeneProduct373117 (Entrez Gene)
ddx1GeneProductENSDARG00000032117 (Ensembl)
ddx20GeneProduct556273 (Entrez Gene)
dhx15GeneProduct321931 (Entrez Gene)
dhx16GeneProduct336645 (Entrez Gene)
dhx8GeneProductENSDARG00000054707 (Ensembl)
dicer1GeneProduct324724 (Entrez Gene)
fusGeneProduct394058 (Entrez Gene)
hnrnpa3GeneProductENSDARG00000059351 (Ensembl) HNRPA3 is old identifier for HNRNPA3
hnrnpcGeneProductENSDARG00000053810 (Ensembl) HNRPC is old identifier for hnrnpc
hnrnpdGeneProductENSDARG00000059246 (Ensembl)
hnrnph1lGeneProduct321556 (Entrez Gene)
hnrnpkGeneProduct406267 (Entrez Gene)
hnrnpmGeneProductENSDARG00000061735 (Ensembl)
hnrnprGeneProductENSDARG00000014569 (Ensembl)
hnrpa1GeneProduct378453 (Entrez Gene)
hnrpabGeneProduct321466 (Entrez Gene)
hnrplGeneProduct394074 (Entrez Gene)
hnrpuGeneProduct334490 (Entrez Gene)
lsm7GeneProduct573047 (Entrez Gene)
mettl3 GeneProduct100004398 (Entrez Gene)
narGeneProduct30203 (Entrez Gene)
ncbp2GeneProduct192325 (Entrez Gene)
nonoGeneProduct321994 (Entrez Gene)
nxf1GeneProduct323865 (Entrez Gene)
pabn1GeneProduct406543 (Entrez Gene)
papolaGeneProduct404041 (Entrez Gene)
pcbp2GeneProduct321844 (Entrez Gene)
phf5aGeneProduct286774 (Entrez Gene)
ppm1gGeneProduct368275 (Entrez Gene) PMID: 12773558
prmt1GeneProduct321974 (Entrez Gene)
prmt2GeneProduct558841 (Entrez Gene)
prpf18GeneProduct431751 (Entrez Gene)
prpf3GeneProduct403072 (Entrez Gene)
prpf40aGeneProduct321555 (Entrez Gene) Alias for FNBP3
prpf4GeneProduct326944 (Entrez Gene)
prpf4bbGeneProduct406758 (Entrez Gene)
ptbp1aGeneProduct323490 (Entrez Gene)
ptbp2aGeneProductENSDARG00000101947 (Ensembl)
ptbp2bGeneProductENSDARG00000015901 (Ensembl)
rbm17GeneProduct393889 (Entrez Gene)
rbm5GeneProductENSDARG00000098280 (Ensembl)
rngttGeneProduct405803 (Entrez Gene)
rnpc2GeneProduct406251 (Entrez Gene)
rnps1GeneProduct327020 (Entrez Gene) PMID: 14729963
sf3a1GeneProductENSDARG00000041887 (Ensembl)
sf3a2GeneProduct394018 (Entrez Gene)
sf3b1GeneProduct446117 (Entrez Gene)
sf3b2GeneProductENSDARG00000018049 (Ensembl)
sf3b4GeneProduct192318 (Entrez Gene)
sf3b5GeneProduct436751 (Entrez Gene)
sfpqGeneProduct406564 (Entrez Gene)
sfrs10GeneProduct394172 (Entrez Gene)
sfrs16GeneProduct555304 (Entrez Gene)
sfrs1GeneProductENSDARG00000017843 (Ensembl) Antagonist splicing factor
sfrs3GeneProduct368925 (Entrez Gene)
sfrs5aGeneProductENSDARG00000029818 (Ensembl)
sfrs5bGeneProductENSDARG00000027734 (Ensembl)
sfrs6aGeneProductENSDARG00000013729 (Ensembl)
sfrs6bGeneProductENSDARG00000016783 (Ensembl)
sfswapGeneProduct394143 (Entrez Gene)
smc1alGeneProductENSDARG00000058203 (Ensembl)
smx5GeneProduct57924 (Entrez Gene)
snrp70GeneProduct445398 (Entrez Gene)
snrpa1GeneProduct492511 (Entrez Gene)
snrpaGeneProduct324121 (Entrez Gene)
snrpb2GeneProduct402896 (Entrez Gene)
snrpbGeneProduct402966 (Entrez Gene) snrpb is the zebrafish homolog of human SNRPN
snrpd1GeneProduct192331 (Entrez Gene)
snrpd2GeneProduct550244 (Entrez Gene)
snrpeGeneProduct393979 (Entrez Gene)
snrpflGeneProduct445404 (Entrez Gene)
snrpgGeneProduct447922 (Entrez Gene)
spopGeneProduct100005514 (Entrez Gene)
srek1GeneProduct445219 (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.
srp54GeneProduct393963 (Entrez Gene) PMID: 14729963
srpk1GeneProduct323679 (Entrez Gene) PMID: 12773558
srrm1GeneProduct406751 (Entrez Gene)
srsf10aGeneProductENSDARG00000022415 (Ensembl)
srsf10bGeneProductENSDARG00000086411 (Ensembl)
srsf2bGeneProduct323700 (Entrez Gene)
srsf7aGeneProduct402972 (Entrez Gene)
srsf9GeneProduct405835 (Entrez Gene) PMID: 12738786, PMID: 12024014 (associated with hnRNP A1 splicing)
ssfa1GeneProductENSDARG00000023299 (Ensembl) Alias of snu13b
sugp1GeneProductENSDARG00000075936 (Ensembl)
  • inferred from: SURP 2, G patch protein, UniProt:O60378
  • SF4 is alias for sugp1; added annotation
supt5hGeneProduct64275 (Entrez Gene)
tmed10GeneProduct326716 (Entrez Gene)
txnl4aGeneProduct449780 (Entrez Gene)
u2af1GeneProduct192328 (Entrez Gene)
wdr57GeneProduct393292 (Entrez Gene)
xrn2GeneProduct321940 (Entrez Gene)
ybx1GeneProductENSDARG00000004757 (Ensembl)
zgc:55440GeneProduct406824 (Entrez Gene)
zgc:77804GeneProduct402989 (Entrez Gene)

Annotated Interactions

No annotated interactions
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