Deadenylation-dependent mRNA decay (Homo sapiens)

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2, 15, 18, 19, 33...2, 10, 15, 16, 18...2, 15, 17-20, 31...412, 8, 15, 17-19, 24...2, 6, 14, 15, 18...2, 15, 18, 19, 23...1, 2, 9, 15, 18...2, 3, 5, 15, 18...2, 5, 15, 18, 19, 21...cytosolmature mRNA (eukaryotic, capped and polyadenylated) PATL1 PATL1 Exosome ComplexPABPC1 EIF4ELSM5 NT5C3BCNOT3 DCP1A PAN2-PAN3 ComplexLSM4 7-MeGDPEIF4A1 LSM2 EDC4 DCP1-DCP2 DecappingComplexH2OEIF4A2 LSM6 CNOT6L CNOT7 AMPDCP2 PATL1 LSM3 CCR4-NOT ComplexPARN Decapped mRNA:LSM1-7ComplexEIF4E CMPPiEIF4G1XRN1LSM1 mature mRNA(eukaryotic, cappedand deadenylated)LSM4 EXOSC3 7MGUMPPAIP1EIF4A2 EXOSC1 EIF4B LSM2 H2OPartiallyDeadenylated mRNAComplexEDC3 LSM2 TNKS1BP1 EIF4A1 EIF4B LSM6 H2OCNOT1 CNOT2 RQCD1 EIF4A3 LSM7 LSM1 PAN3 H2OEXOSC2 AMPTranslatable mRNAComplexLSM6 PARN homodimermature mRNA (eukaryotic, capped and deadenylated) EXOSC4 PAIP1 LSM4 EIF4A3 DDX6 CNOT4 DCP1B EIF4E LSM7 CNOT10 LSM7 CMPEIF4G1 AMPLsm1-7 ComplexPAN2 EXOSC8 LSM5 DIS3 EXOSC6 mature mRNA (eukaryotic, capped and partially deadenylated) H2OH2OEIF4A1 GMPEXOSC5 AMPLSM1 DCPSEXOSC7 PABPC1EIF4G1 7MGMPPAIP1 DeadenylatedmRNA:Lsm1-7 ComplexEIF4BLSM3 H2OEIF4A2 CNOT6 oligoribonucleotidewith a5'-diphosphatePABPC1 cappedoligoribonucleotideUMPLSM5 decapped mRNA with 5' monophosphate CNOT11 eIF4AGMPEIF4A3 LSM3 CNOT8 EXOSC9 74, 29, 4413, 20, 25, 362827, 3811, 1242


Description

After undergoing rounds of translation, mRNA is normally destroyed by the deadenylation-dependent pathway. Though the trigger is unclear, deadenylation likely proceeds in two steps: one catalyzed by the PAN2-PAN3 complex that shortens the poly(A) tail from about 200 adenosine residues to about 80 residues and one catalyzed by the CCR4-NOT complex or by the PARN enzyme that shortens the tail to about 10-15 residues.
After deadenylation the mRNA is then hydrolyzed by either the 5' to 3' pathway or the 3' to 5' pathway. It is unknown what determinants target a mRNA to one pathway or the other.
The 5' to 3' pathway is initiated by binding of the Lsm1-7 complex to the 3' oligoadenylate tail followed by decapping by the DCP1-DCP2 complex. The 5' to 3' exoribonuclease XRN1 then hydrolyzes the remaining RNA.
The 3' to 5' pathway is initiated by the exosome complex at the 3' end of the mRNA. The exosome processively hydrolyzes the mRNA from 3' to 5', leaving only a capped oligoribonucleotide. The cap is then removed by the scavenging decapping enzyme DCPS. View original pathway at:Reactome.

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Bibliography

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  1. Wu M, Reuter M, Lilie H, Liu Y, Wahle E, Song H.; ''Structural insight into poly(A) binding and catalytic mechanism of human PARN.''; PubMed Europe PMC Scholia
  2. Bail S, Kiledjian M.; ''More than 1 + 2 in mRNA decapping.''; PubMed Europe PMC Scholia
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  7. Zheng D, Ezzeddine N, Chen CY, Zhu W, He X, Shyu AB.; ''Deadenylation is prerequisite for P-body formation and mRNA decay in mammalian cells.''; PubMed Europe PMC Scholia
  8. Gallie DR.; ''A tale of two termini: a functional interaction between the termini of an mRNA is a prerequisite for efficient translation initiation.''; PubMed Europe PMC Scholia
  9. Ingelfinger D, Arndt-Jovin DJ, Lührmann R, Achsel T.; ''The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and Xrnl in distinct cytoplasmic foci.''; PubMed Europe PMC Scholia
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  11. Fritz DT, Bergman N, Kilpatrick WJ, Wilusz CJ, Wilusz J.; ''Messenger RNA decay in mammalian cells: the exonuclease perspective.''; PubMed Europe PMC Scholia
  12. Fenger-Grøn M, Fillman C, Norrild B, Lykke-Andersen J.; ''Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping.''; PubMed Europe PMC Scholia
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  15. Houseley J, Tollervey D.; ''The many pathways of RNA degradation.''; PubMed Europe PMC Scholia
  16. Lau NC, Kolkman A, van Schaik FM, Mulder KW, Pijnappel WW, Heck AJ, Timmers HT.; ''Human Ccr4-Not complexes contain variable deadenylase subunits.''; PubMed Europe PMC Scholia
  17. Uchida N, Hoshino S, Katada T.; ''Identification of a human cytoplasmic poly(A) nuclease complex stimulated by poly(A)-binding protein.''; PubMed Europe PMC Scholia
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  19. Gao M, Fritz DT, Ford LP, Wilusz J.; ''Interaction between a poly(A)-specific ribonuclease and the 5' cap influences mRNA deadenylation rates in vitro.''; PubMed Europe PMC Scholia
  20. Ozgur S, Chekulaeva M, Stoecklin G.; ''Human Pat1b connects deadenylation with mRNA decapping and controls the assembly of processing bodies.''; PubMed Europe PMC Scholia
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  22. Borman AM, Michel YM, Malnou CE, Kean KM.; ''Free poly(A) stimulates capped mRNA translation in vitro through the eIF4G-poly(A)-binding protein interaction.''; PubMed Europe PMC Scholia
  23. Dupressoir A, Morel AP, Barbot W, Loireau MP, Corbo L, Heidmann T.; ''Identification of four families of yCCR4- and Mg2+-dependent endonuclease-related proteins in higher eukaryotes, and characterization of orthologs of yCCR4 with a conserved leucine-rich repeat essential for hCAF1/hPOP2 binding.''; PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
115026view16:56, 25 January 2021ReactomeTeamReactome version 75
113471view11:54, 2 November 2020ReactomeTeamReactome version 74
112670view16:06, 9 October 2020ReactomeTeamReactome version 73
101587view11:45, 1 November 2018ReactomeTeamreactome version 66
101123view21:29, 31 October 2018ReactomeTeamreactome version 65
100651view20:03, 31 October 2018ReactomeTeamreactome version 64
100201view16:48, 31 October 2018ReactomeTeamreactome version 63
99752view15:14, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99316view12:46, 31 October 2018ReactomeTeamreactome version 62
93995view13:50, 16 August 2017ReactomeTeamreactome version 61
93604view11:28, 9 August 2017ReactomeTeamreactome version 61
87169view19:22, 18 July 2016MkutmonOntology Term : 'pathway pertinent to DNA replication and repair, cell cycle, maintenance of genomic integrity, RNA and protein biosynthesis' added !
86710view09:24, 11 July 2016ReactomeTeamreactome version 56
83258view10:34, 18 November 2015ReactomeTeamVersion54
81369view12:53, 21 August 2015ReactomeTeamVersion53
76837view08:06, 17 July 2014ReactomeTeamFixed remaining interactions
76541view11:52, 16 July 2014ReactomeTeamFixed remaining interactions
75874view09:52, 11 June 2014ReactomeTeamRe-fixing comment source
75574view10:39, 10 June 2014ReactomeTeamReactome 48 Update
74929view13:45, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74573view08:37, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
7-MeGDPMetaboliteCHEBI:20794 (ChEBI)
7MGMetaboliteCHEBI:20794 (ChEBI)
7MGMPMetaboliteCHEBI:17825 (ChEBI)
AMPMetaboliteCHEBI:16027 (ChEBI)
CCR4-NOT ComplexComplexR-HSA-429896 (Reactome) The human CCR4-NOT complex contains 7 core subunits: CNOT1, CNOT2, CNOT3, CNOT9/RCD1, CNOT10, TAB182, and C2ORF29. Complexes contain either CNOT7 or CNOT8 (with CNOT8-containing complexes apparently involved in nuclear RNA splicing and CNOT7-containing complexes involved in cytoplasmic mRNA decay) and CNOT6 or CNOT6L. CNOT6 and CNOT6L are catalytic exoribonucleases. CNOT7 and CNOT8 also have ribonuclease activity. CNOT1 is the largest subunit and, based on yeast two-hybrid assays, interacts with CNOT2, CNOT7, CNOT8, and CNOT9, thus acting as a scaffold.
CMPMetaboliteCHEBI:17361 (ChEBI)
CNOT1 ProteinA5YKK6 (Uniprot-TrEMBL)
CNOT10 ProteinQ9H9A5 (Uniprot-TrEMBL)
CNOT11 ProteinQ9UKZ1 (Uniprot-TrEMBL)
CNOT2 ProteinQ9NZN8 (Uniprot-TrEMBL)
CNOT3 ProteinO75175 (Uniprot-TrEMBL)
CNOT4 ProteinO95628 (Uniprot-TrEMBL)
CNOT6 ProteinQ9ULM6 (Uniprot-TrEMBL)
CNOT6L ProteinQ96LI5 (Uniprot-TrEMBL)
CNOT7 ProteinQ9UIV1 (Uniprot-TrEMBL)
CNOT8 ProteinQ9UFF9 (Uniprot-TrEMBL)
DCP1-DCP2 Decapping ComplexComplexR-HSA-429991 (Reactome)
DCP1A ProteinQ9NPI6 (Uniprot-TrEMBL)
DCP1B ProteinQ8IZD4 (Uniprot-TrEMBL)
DCP2 ProteinQ8IU60 (Uniprot-TrEMBL)
DCPSProteinQ96C86 (Uniprot-TrEMBL)
DDX6 ProteinP26196 (Uniprot-TrEMBL)
DIS3 ProteinQ9Y2L1 (Uniprot-TrEMBL)
Deadenylated mRNA:Lsm1-7 ComplexComplexR-HSA-429908 (Reactome)
Decapped mRNA:LSM1-7 ComplexComplexR-HSA-429996 (Reactome)
EDC3 ProteinQ96F86 (Uniprot-TrEMBL)
EDC4 ProteinQ6P2E9 (Uniprot-TrEMBL)
EIF4A1 ProteinP60842 (Uniprot-TrEMBL)
EIF4A2 ProteinQ14240 (Uniprot-TrEMBL)
EIF4A3 ProteinP38919 (Uniprot-TrEMBL)
EIF4B ProteinP23588 (Uniprot-TrEMBL)
EIF4BProteinP23588 (Uniprot-TrEMBL)
EIF4E ProteinP06730 (Uniprot-TrEMBL)
EIF4EProteinP06730 (Uniprot-TrEMBL)
EIF4G1 ProteinQ04637 (Uniprot-TrEMBL)
EIF4G1ProteinQ04637 (Uniprot-TrEMBL)
EXOSC1 ProteinQ9Y3B2 (Uniprot-TrEMBL)
EXOSC2 ProteinQ13868 (Uniprot-TrEMBL)
EXOSC3 ProteinQ9NQT5 (Uniprot-TrEMBL)
EXOSC4 ProteinQ9NPD3 (Uniprot-TrEMBL)
EXOSC5 ProteinQ9NQT4 (Uniprot-TrEMBL)
EXOSC6 ProteinQ5RKV6 (Uniprot-TrEMBL)
EXOSC7 ProteinQ15024 (Uniprot-TrEMBL)
EXOSC8 ProteinQ96B26 (Uniprot-TrEMBL)
EXOSC9 ProteinQ06265 (Uniprot-TrEMBL)
Exosome ComplexComplexR-HSA-429971 (Reactome) The exosome complex comprises a ring and associated subunits. The ring contains EXOSC2, EXOSC7, EXOSC8, EXOSC9, EXOSC5, and EXOSC6. The subunits EXOSC1, EXOSC2, EXOSC3, and RRP44 bind the ring. The catalytic ribonuclease site is located in RRP44, which yields ribonucleotides having 5'-monophosphates.
GMPMetaboliteCHEBI:17345 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
LSM1 ProteinO15116 (Uniprot-TrEMBL)
LSM2 ProteinQ9Y333 (Uniprot-TrEMBL)
LSM3 ProteinP62310 (Uniprot-TrEMBL)
LSM4 ProteinQ9Y4Z0 (Uniprot-TrEMBL)
LSM5 ProteinQ9Y4Y9 (Uniprot-TrEMBL)
LSM6 ProteinP62312 (Uniprot-TrEMBL)
LSM7 ProteinQ9UK45 (Uniprot-TrEMBL)
Lsm1-7 ComplexComplexR-HSA-430001 (Reactome)
NT5C3BProteinQ969T7 (Uniprot-TrEMBL)
PABPC1 ProteinP11940 (Uniprot-TrEMBL)
PABPC1ProteinP11940 (Uniprot-TrEMBL)
PAIP1 ProteinQ9H074 (Uniprot-TrEMBL)
PAIP1ProteinQ9H074 (Uniprot-TrEMBL)
PAN2 ProteinQ504Q3 (Uniprot-TrEMBL)
PAN2-PAN3 ComplexComplexR-HSA-429882 (Reactome)
PAN3 ProteinQ58A45 (Uniprot-TrEMBL)
PARN ProteinO95453 (Uniprot-TrEMBL)
PARN homodimerComplexR-HSA-429886 (Reactome) Structural analysis has shown that PARN forms homodimers.
PATL1 ProteinQ86TB9 (Uniprot-TrEMBL)
Partially

Deadenylated mRNA

Complex		ComplexR-HSA-429989 (Reactome)
PiMetaboliteCHEBI:18367 (ChEBI)
RQCD1 ProteinQ92600 (Uniprot-TrEMBL)
TNKS1BP1 ProteinQ9C0C2 (Uniprot-TrEMBL)
Translatable mRNA ComplexComplexR-HSA-429977 (Reactome) mRNA's that are ready for translation have a circular structure caused by interaction between PABP bound to the 3' poly(A) tail and the eIF4E-eIF4G-PAIP complex bound to the 7-methylguanosine cap. The interaction between poly(A)-PABP and the eIF4G-eIF4E complex stimulates affinity of eIF4E for the cap and improves translation.
UMPMetaboliteCHEBI:16695 (ChEBI)
XRN1ProteinQ8IZH2 (Uniprot-TrEMBL)
capped oligoribonucleotideR-NUL-429926 (Reactome)
decapped mRNA with 5' monophosphate R-NUL-429875 (Reactome)
eIF4AComplexR-HSA-429842 (Reactome)
mature mRNA

(eukaryotic, capped

and deadenylated)		R-NUL-429974 (Reactome) After deadenylation, mRNAs have 10-15 3' adenosine residues remaining of about 200 initial adenosine residues.
mature mRNA (eukaryotic, capped and deadenylated) R-NUL-429974 (Reactome) After deadenylation, mRNAs have 10-15 3' adenosine residues remaining of about 200 initial adenosine residues.
mature mRNA (eukaryotic, capped and partially deadenylated) R-NUL-429909 (Reactome) A partially deadenylated mRNA has about 80 3' adenosine residues remaining of about 200 initial adenosine residues..
mature mRNA (eukaryotic, capped and polyadenylated) R-NUL-430014 (Reactome) A mature, translatable mRNA has a 5' cap structure and 3' polyadenylation. The cap comprises 7-methylguanosine triphosphate linked 5' to 5' to the first ribonucleotide residue of the mRNA. About 200 adenosine residues are polymerized at the 3' end.
oligoribonucleotide

with a

5'-diphosphate		R-NUL-429925 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
7-MeGDPArrowR-HSA-429860 (Reactome)
7MGArrowR-HSA-5694126 (Reactome)
7MGMPArrowR-HSA-429961 (Reactome)
7MGMPR-HSA-5694126 (Reactome)
AMPArrowR-HSA-429845 (Reactome)
AMPArrowR-HSA-429955 (Reactome)
AMPArrowR-HSA-429992 (Reactome)
AMPArrowR-HSA-430021 (Reactome)
AMPArrowR-HSA-430028 (Reactome)
CCR4-NOT Complexmim-catalysisR-HSA-429955 (Reactome)
CMPArrowR-HSA-429845 (Reactome)
CMPArrowR-HSA-430028 (Reactome)
DCP1-DCP2 Decapping Complexmim-catalysisR-HSA-429860 (Reactome)
DCPSmim-catalysisR-HSA-429961 (Reactome)
Deadenylated mRNA:Lsm1-7 ComplexArrowR-HSA-429978 (Reactome)
Deadenylated mRNA:Lsm1-7 ComplexR-HSA-429860 (Reactome)
Decapped mRNA:LSM1-7 ComplexArrowR-HSA-429860 (Reactome)
Decapped mRNA:LSM1-7 ComplexR-HSA-429845 (Reactome)
EIF4BArrowR-HSA-429955 (Reactome)
EIF4BArrowR-HSA-429992 (Reactome)
EIF4EArrowR-HSA-429955 (Reactome)
EIF4EArrowR-HSA-429992 (Reactome)
EIF4G1ArrowR-HSA-429955 (Reactome)
EIF4G1ArrowR-HSA-429992 (Reactome)
Exosome Complexmim-catalysisR-HSA-430028 (Reactome)
GMPArrowR-HSA-429845 (Reactome)
GMPArrowR-HSA-430028 (Reactome)
H2OR-HSA-429845 (Reactome)
H2OR-HSA-429860 (Reactome)
H2OR-HSA-429955 (Reactome)
H2OR-HSA-429961 (Reactome)
H2OR-HSA-429992 (Reactome)
H2OR-HSA-430021 (Reactome)
H2OR-HSA-430028 (Reactome)
H2OR-HSA-5694126 (Reactome)
Lsm1-7 ComplexArrowR-HSA-429845 (Reactome)
Lsm1-7 ComplexR-HSA-429978 (Reactome)
NT5C3Bmim-catalysisR-HSA-5694126 (Reactome)
PABPC1ArrowR-HSA-429955 (Reactome)
PABPC1ArrowR-HSA-429992 (Reactome)
PAIP1ArrowR-HSA-429955 (Reactome)
PAIP1ArrowR-HSA-429992 (Reactome)
PAN2-PAN3 Complexmim-catalysisR-HSA-430021 (Reactome)
PARN homodimermim-catalysisR-HSA-429992 (Reactome)
Partially

Deadenylated mRNA

Complex		ArrowR-HSA-430021 (Reactome)
Partially

Deadenylated mRNA

Complex		R-HSA-429955 (Reactome)
Partially

Deadenylated mRNA

Complex		R-HSA-429992 (Reactome)
PiArrowR-HSA-5694126 (Reactome)
R-HSA-429845 (Reactome) The XRN1 exoribonuclease hydrolyzes decapped mRNA from 5' to 3' and yields ribonucleotides having 5'-monophosphates. In yeast Xrn1 associates with the Lsm1-7 complex.
R-HSA-429860 (Reactome) The DCP1-DCP2 decapping complex binds the 7-methylguanosine cap of mRNA and hydrolyzes the triphosphate bond to yield 7-methylguanosine 5'-diphosphate and RNA with 5'-monophosphate. The DCP2 subunit of the complex catalyzes the hydrolysis. DCP2 has higher affinity for some subsets of mRNA.
R-HSA-429955 (Reactome) The CCR4-NOT complex hydrolyzes adenosine residues at the 3' end of polyadenylated mRNA, shortening the number of adenosine residues to about 10-15 residues and yielding adenosine 5'-monophosphate. CNOT6 and CNOT6L are the exoribonucleases responsible for hydrolysis. Activity of the CCR4-NOT complex is inhibited by PABP bound to the poly(A) tail of the mRNA. The trigger for activation of deadenylation by the CCR4-NOT complex is unknown. Complexes containing CNOT7 rather than CNOT8 appear to be responsible for cytoplasmic mRNA decay.
R-HSA-429961 (Reactome) The scavenging nuclease DCPS hydrolyzes the triphosphate bond between the 7-methylguanosine cap and the remaining oligoribonucleotide body of the mRNA. The products are 7-methylguanosine 5'-monophosphate and an oligoribonucleotide with a 5'-diphosphate.
R-HSA-429978 (Reactome) The Lsm1-7 complex forms a heptameric ring that binds the 3' oligoadenylated ends of mRNAs that have been deadenylated. The bound Lsm1-7 may prevent access of the exosome (a 3' to 5' exonuclease) to the 3' end and thereby direct the mRNA to the 5' to 3' exonuclease pathway. The yeast Lsm1-7 complex has a preference for oligoadenylated RNA compared to polyadenylated RNA, however other determinants of binding by Lsm1-7 are unknown.
R-HSA-429992 (Reactome) The PARN exoribonuclease hydrolyzes adenosine residues at the 3' ends of polyadenylated mRNA, shortening the poly(A) tail from about 80 adenosine residues to about 10-15 residues and yielding adenosine 5'-monophosphate. PARN interacts simultaneously with the poly(A) tail and with the 7-methylguanosine cap of the mRNA, therefore it is believed that PARN displaces the eIF4F cap-binding complex. The trigger for deadenylation by PARN is unknown. PARN is also part of a complex that regulates poly(A) tail length and hence translation in developing oocytes.
R-HSA-430021 (Reactome) The PAN2-PAN3 exoribonuclease complex hydrolyzes the poly(A) tail of a mRNA, shortening the tail from about 200 adenosine residues to about 80 adenosine residues and yielding adenosine 5'-monophosphate. PAN2 is the exoribonuclease component of the complex; PAN3 is required for cellular localization. The poly(A)-binding protein (PABP) interacts with PAN3 and recruits the PAN2-PAN3 complex to mRNA.
R-HSA-430028 (Reactome) The exosome complex hydrolyzes capped, deadenylated mRNA from 3' to 5' and yields ribonucleotides having 5'-monophosphates. In yeast the Ski2-Ski3-Ski8 complex assists degradation by the exosome complex, however little is known about the function of the homologous Ski complex in mammals. Although many exosomal components contain exonuclease signatures, only two components have been shown to degrade RNA. Rrp6/PMSCL-100 has been shown to be involved in the 3’-5’ decay of nuclear mRNAs in yeast. Rrp6 may also function in the absence of the core exosomal components. The Rrp44/dDis3 component of the core exosome has been shown to possess both 3’-5’ exonuclease activity along with endonuclease activity via its PIN domain.
R-HSA-5694126 (Reactome) Cytosolic 7-methylguanosine phosphate-specific 5'-nucleotidase (NT5C3B) specifically hydrolyses N(7)-methylguanosine monophosphate (7MGMP) to 7-methylguanosine (7MG) and inorganic phosphate (Pi). 7MGP is a modified nucleotide byproduct of mRNA turnover and requires degradation as its incorporation into nucleic acids is undesirable (Buschmann et al. 2013).
Translatable mRNA ComplexR-HSA-430021 (Reactome)
UMPArrowR-HSA-429845 (Reactome)
UMPArrowR-HSA-430028 (Reactome)
XRN1mim-catalysisR-HSA-429845 (Reactome)
capped oligoribonucleotideArrowR-HSA-430028 (Reactome)
capped oligoribonucleotideR-HSA-429961 (Reactome)
eIF4AArrowR-HSA-429955 (Reactome)
eIF4AArrowR-HSA-429992 (Reactome)
mature mRNA

(eukaryotic, capped

and deadenylated)		ArrowR-HSA-429955 (Reactome)
mature mRNA

(eukaryotic, capped

and deadenylated)		ArrowR-HSA-429992 (Reactome)
mature mRNA

(eukaryotic, capped

and deadenylated)		R-HSA-429978 (Reactome)
mature mRNA

(eukaryotic, capped

and deadenylated)		R-HSA-430028 (Reactome)
oligoribonucleotide

with a

5'-diphosphate		ArrowR-HSA-429961 (Reactome)
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