mRNA Processing (Homo sapiens)

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1CF Isplicesome associated helicasesU2 snRNPsPolr2a5'exon 1AFormation of the Spliceosomal B complex3'35Poly(A)pb IICA(2)Formation of the active Spliceosomal C complexARngtt (capping enzyme)(1)P-3'SF3b14bSR-repressor proteins3'exon 1AGU6YYYYU1 snRNPexon 2U2CFI3'Poly(A) polymerase alphaPutative Alternative SplicingRegulatorsInternal methylation of mRNAmRNA polyadenylation5'Additional FactorsU4 snRNPmRNA cappingGUSR-proteinsCleavage of mRNA at the 3'-endYYYYFormation of the Spliceosomal C complex(3)Formation of pre-mRNPsiPoRnmt (methyltransferase)(2a)mRNA 3'-end processingProcessing of Intron-Containing Pre-mRNAAAAAAAAU5SR protein phosphatasesexon 2Cap BindingsnRNP Sm core complexU6 snRNPNote: New participating members shown at each stepexon 2SR-phosphatasesSR-proteins3'YYYYU2 snRNPYYYY5'65U5 snRNPA5'AGexon 2AmRNA splice site selectionAGFormation of the Spliceosomal B complexU53'3'YYYYAdditional SR proteinsAFormation of the Spliceosomal E complexSR protein kinasesRNAi pathwaymRNA CappingRNA helicase AFormation of the Spliceosomal E complexexon 1Formation of the Spliceosomal A complexCPSFCF IIRNA helicaseA3'SR-binding sitesPoly(A)-binding protein IIexon 2AGMethylation of mRNAPoly(A) pol5' G capSR-proteinsU4/U6AAUAAAdegradedsnRNP Sm core complex5'Cleavage at the 3'-Splice-Site and Exon LigationPrimary RNA transcriptCstF5'U2AFKinases Phosphorylating RS domains?Accessory ProteinsU1exon 1(2b)SR-kinases5'UG5'Regulation ofAlternative Splicingright click on blue text for detailed informationCstFhnRNPsLariat Formation and 5'-Splice Site CleavageFormation of pre-mRNPssnRNP Sm core complex5'Additional FactorsYYYY(2c)Piheterogeneous nuclear ribonucleoproteinsintronCPSFAGexon 1Misc.exon 2U4:U5:U6 tri-snRNP complexpre-mRNAU4Serine/Argenine Rich Proteins(SR)3'hnRNP regulatorsSR-binding sitesU2AFSpt5splicing factor SF3B5'AGCF IIUG3'Formation of the Spliceosomal A complexPU2 snRNP3'splicing factor SF3A5'exon 1Internal methylation of mRNAAdditional FactorsU1 snRNPmRNA splicing (major pathway)SSFA1CDC40ATPSRRM1CDC40PRPF18DHX16Rnu6RNPS1BRUNOL4TMP21CPSF1SFRS5SNRP70XRN2RBM5WDR57SF3A1DHX8FUSIP1SSFA1HNRPH2SNRPNSNRPBFNBP3PHF5AGMPU1 snRNARBMXNONOSNRPD3HNRPA3P1SF3B1CPSF3CSTF2CSTF2THRMT1L2SFRS12CLK1HNRPDDHX9SRPK2PRPF4HNRPKHNRPH1HNRPLFUSIP1CUGBP2SF4SFRS14NXF1CPSF2PCBP2LSM2SNRPD1PTBP1SFPQDNAJC8SF3A3POLR2APRPF4SNRPASNRPGU5 snRNALSM2FUSHEABHNRPUSPOPHNRPMPTBP2PRPF8SFRS7PSKH1RNGTTPAPOLAU2AF2SRP54CSTF1RNU2DICER1SMC1L1DHX38SFRS6CPSF4CUGBP1SNRPA1HNRPCU2AF1HNRPA1RBM17HRMT1L1NCBP2SFRS10C20orf14RNPC2DHX15SRPK1HNRPA2B1NUDT21RNMTSF3B3HNRPRLSM7SNRPB2SFRS4U4 snRNASNRPNU5-116KDPRPF4BSFRS2SFRS16SNRPESF3A2CD2BP2SF3B2PPM1GTXNL4ASNRPD2SFRS1PABPN1CLK2NCBP1DDX1SSFA1DDX20PRPF3SFRS8CLK4SF3B5NSEP1CLK3METTL3SNRPFHNRPABSF3B4PRPF8SUPT5HSFRS9CSTF3SFRS3


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:

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


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96893view13:50, 18 April 2018FehrhartFixed minor graphical issues
96288view21:54, 6 March 2018Andrewlmasonnone
95128view15:26, 16 November 2017Mkutmonremoved nested groups
94839view15:55, 6 October 2017Khanspersconverted interactions to graphical lines
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67498view11:09, 26 June 2013DdiglesOntology Term : 'spliceosome pathway' added !
45374view21:22, 7 October 2011Khansperscleaned up description and removed old comment
44924view10:51, 6 October 2011MartijnVanIerselOntology Term : 'transcription pathway' added !
41073view23:19, 1 March 2011MaintBotRemoved redundant pathway information and comments
38901view20:24, 24 September 2010AlexanderPicominor tweaks
38872view18:29, 24 September 2010Khanspers
35228view18:39, 11 February 2010KhanspersChanged snRNAs from Other to RNA
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35122view13:25, 11 February 2010MartijnVanIerseladded lit. ref.
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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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