BioPAX pathway converted from "ZCCHC6, ZCCHC11 are mRNA uridyltransferases" in the Reactome database.LEFT-TO-RIGHT2.7.7.52ZCCHC6, ZCCHC11 are mRNA uridyltransferasesUridylyltransferases mediates the terminal uridylation of mRNAs, RISC-cleaved transcripts and of various non-coding RNAs including miRNAs and their precursors mRNAs (Scott and Norbury 2013, Lee et al. 2014, Munoz-Tello et al. 2015, Scheer et al. 2016). TUT4 and TUT7 (ZCCHC11, ZCCHC6) are mRNA uridylation enzymes that can act on the majority of mammalian mRNAs (Lim et al. 2014). More than 85% of mRNAs are uridylated at a frequency of higher than 1% in NIH 3T3 and HeLa cells (Chang et al. 2014). Uridylated tails were found mainly on mRNAs with polyA tails of less than 25 nucleotides, suggesting that uridylation may occur after deadenylation. There was a negative correlation between uridylation frequency and mRNA half‑life, suggesting a role of uridylation in general mRNA decay (Lim et al. 2014).. TUT4 and TUT7 (ZCCHC11, ZCCHC6) also uridylate replication-dependent histone mRNAs, which are not polyadenylated, to facilitate their degradation (Lackey et al 2016, Schmidt et al. 2011, Mullen & Marzluff 2008, Hoefig et al. 2013, Slevin et al. 2014). TUT4 and TUT7 also uridylate miRNAs and their precursors (Thornton et al. 2014, Lee et al. 2014, Ha & Kim 2014). Mono-uridylation of pre-miRNA facilitates miRNA processing, while polyuridylation of pre-miRNA triggers their degradation (Heo et al. 2012).Authored: Jupe, Steve, 2016-09-30Reviewed: Gagliardi, Dominique, 2017-02-06Edited: Jupe, Steve, 2017-02-02uridine residueReactome DB_ID: 6782337cytosolGENE ONTOLOGYGO:0005829uridine residue [ChEBI:73747]uridine residueChEBICHEBI:73747Reactome Database ID Release 716782337Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=6782337ReactomeR-ALL-67823372Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-6782337.2Reactomehttp://www.reactome.orgPartially Deadenylated mRNA ComplexReactome DB_ID: 429989PAIP1Polyadenylate-binding protein-interacting protein 1PAIP1_HUMANReactome DB_ID: 429861UniProt:Q9H074 PAIP1PAIP1FUNCTION Acts as a coactivator in the regulation of translation initiation of poly(A)-containing mRNAs. Its stimulatory activity on translation is mediated via its action on PABPC1. Competes with PAIP2 for binding to PABPC1. Its association with EIF4A and PABPC1 may potentiate contacts between mRNA termini. May also be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain.SUBUNIT Interacts with the RRM1-RRM2 and C-terminus regions of PABPC1 in a 1:1 stoichiometry. Interacts with EIF4A.DOMAIN Only the PABPC1-interacting motif-1 (PAM1) stimulates translation initiation.Homo sapiensNCBI Taxonomy9606UniProtQ9H0741EQUAL479EQUALReactome Database ID Release 71429861Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429861ReactomeR-HSA-4298611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429861.11EIF4EeIF4EeIF-4F 25 kDa subuniteukaryotic translation initiation factor 4EmRNA cap-binding proteinEukaryotic translation initiation factor 4EeIF-4EReactome DB_ID: 72578UniProt:P06730 EIF4EEIF4EEIF4EL1EIF4FFUNCTION Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap.SUBUNIT eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. EIF4E is also known to interact with other partners. The interaction with EIF4ENIF1 mediates the import into the nucleus. Hypophosphorylated EIF4EBP1, EIF4EBP2 and EIF4EBP3 compete with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:24207126, PubMed:25533957, PubMed:21661078). Rapamycin can attenuate insulin stimulation, mediated by FKBPs. Interacts mutually exclusive with EIF4A1 or EIF4A2. Interacts with NGDN and PIWIL2. Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1. Interacts directly with CYFIP1. Interacts with CLOCK (By similarity). Binds to MKNK2 in nucleus. Interacts with LIMD1, WTIP and AJUBA. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with LARP1. Interacts with METTL3 (PubMed:27117702). Interacts with RBM24; this interaction prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly of translation initiation complex (PubMed:29358667).SUBUNIT (Microbial infection) Interacts with Lassa virus Z protein.PTM Phosphorylation increases the ability of the protein to bind to mRNA caps and to form the eIF4F complex.DISEASE A chromosomal aberration involving EIF4E has been found in a patient with classic autism. Translocation t(45)(q23q31.3). The breakpoint on chromosome 4 is located 56 kb downstream of EIF4E (PubMed:19556253).SIMILARITY Belongs to the eukaryotic initiation factor 4E family.CAUTION Was originally thought to be phosphorylated on Ser-53 (PubMed:3112145); this was later shown to be wrong (PubMed:7665584).UniProtP067302EQUAL217EQUALReactome Database ID Release 7172578Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72578ReactomeR-HSA-725781Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72578.11P220EIF4G1eIF4GeIF-4-gammaeIF-4Geukaryotic translation initiation factor 4 gammaEukaryotic translation initiation factor 4 gammap220Reactome DB_ID: 72584UniProt:Q04637 EIF4G1EIF4G1EIF4FEIF4GEIF4GIFUNCTION Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome.SUBUNIT eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E (cap-binding) and EIF4G1/EIF4G3. Interacts with eIF3, mutually exclusive with EIF4A1 or EIFA2, EIF4E and through its N-terminus with PAPBC1. Interacts through its C-terminus with the serine/threonine kinases MKNK1, and with MKNK2. Appears to act as a scaffold protein, holding these enzymes in place to phosphorylate EIF4E. Non-phosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. EIF4G1/EIF4G3 interacts with PABPC1 to bring about circularization of the mRNA. Rapamycin can attenuate insulin stimulation mediated by FKBPs. Interacts with EIF4E3. Interacts with CIRBP and MIF4GD. Interacts with RBM4. Interacts with HNRNPD/AUF1; the interaction requires RNA.SUBUNIT (Microbial infection) Interacts with rotavirus A NSP3; in this interaction, NSP3 takes the place of PABPC1 thereby inducing shutoff of host protein synthesis.SUBUNIT (Microbial infection) Interacts with human adenovirus 5 protein 100K; this interaction promotes translational shunt in presence of polysomes containing viral tripartite leader mRNAs.PTM Phosphorylated at multiple sites in vivo. Phosphorylation at Ser-1185 by PRKCA induces binding to MKNK1.PTM Following infection by certain enteroviruses, rhinoviruses and aphthoviruses, EIF4G1 is cleaved by the viral protease 2A, or the leader protease in the case of aphthoviruses. This shuts down the capped cellular mRNA transcription.SIMILARITY Belongs to the eukaryotic initiation factor 4G family.UniProtQ046371EQUAL1599EQUALReactome Database ID Release 7172584Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72584ReactomeR-HSA-725841Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72584.11Converted from EntitySet in ReactomeeIF4AReactome DB_ID: 429842EIF4A1eIF4A-IeIF4AIeIF-4A-Ieukaryotic initiation factor 4A-IEukaryotic initiation factor 4A-IReactome DB_ID: 72573UniProt:P60842 EIF4A1EIF4A1DDX2AEIF4AFUNCTION ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon.ACTIVITY REGULATION Helicase activity and function in translation are inhibited by interaction with PDCD4.SUBUNIT eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. Interacts with PAIP1, EIF4E and UPF2. Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29, VPS35 and SFN. May interact with NOM1. Interacts with PDCD4; this interferes with the interaction between EIF4A and EIF4G. Interacts with RBM4.SUBUNIT (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL69.SIMILARITY Belongs to the DEAD box helicase family. eIF4A subfamily.UniProtP608422EQUAL406EQUALReactome Database ID Release 7172573Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72573ReactomeR-HSA-725731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72573.1EIF4A2eIF4A-IIeIF4AIIeIF-4A-IIeukaryotic initiation factor 4A-IIEukaryotic initiation factor 4A-IIReactome DB_ID: 72575UniProt:Q14240 EIF4A2EIF4A2DDX2BEIF4FFUNCTION ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon.SUBUNIT eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIFFG3 (By similarity). Interacts with EIF4E. May interact with NOM1.SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1/HHV-1 protein Vhs.SIMILARITY Belongs to the DEAD box helicase family. eIF4A subfamily.UniProtQ142401EQUAL407EQUALReactome Database ID Release 7172575Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72575ReactomeR-HSA-725751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72575.1EIF4A3Eukaryotic initiation factor 4A-IIIIF4A3_HUMANReactome DB_ID: 927868UniProt:P38919 EIF4A3EIF4A3DDX48KIAA0111FUNCTION ATP-dependent RNA helicase (PubMed:16170325). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:22961380, PubMed:28502770, PubMed:28076346, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs (PubMed:16209946, PubMed:16170325, PubMed:16314458, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH-RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH-RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the function is different from the established EJC assembly (PubMed:22203037). Involved in craniofacial development (PubMed:24360810).ACTIVITY REGULATION The ATPase activity is increased some 4-fold in the presence of RNA.SUBUNIT Identified in the spliceosome C complex (PubMed:11991638, PubMed:22961380, PubMed:28502770, PubMed:28076346, PubMed:29301961). Core component of the mRNA splicing-dependent exon junction complex (EJC); the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A (PubMed:15034551, PubMed:14730019, PubMed:16170325, PubMed:16314458, PubMed:23917022, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). Interacts with CASC3, MAGOH, NXF1, RBM8A and ALYREF/THOC4 (PubMed:14730019, PubMed:16170325, PubMed:16495234, PubMed:22961380). May interact with NOM1. Interacts with POLDIP3 (PubMed:18423201). Interacts with CWC22 and PRPF19 in an RNA-independent manner (PubMed:22959432, PubMed:22961380, PubMed:23236153, PubMed:24218557). Direct interaction with CWC22 is mediated by the helicase C-terminal domain (PubMed:22959432, PubMed:24218557). Full interaction with CWC22 occurs only when EIF4A3 is not part of the EJC and prevents EIF4A3 binding to RNA. Identified in a complex composed of the EJC core, UPF3B and UPF2. The EJC core can also interact with UPF3A (in vitro) (PubMed:20479275). Interacts with NCBP3 (PubMed:26382858).TISSUE SPECIFICITY Ubiquitously expressed.SIMILARITY Belongs to the DEAD box helicase family. eIF4A subfamily.UniProtP389192EQUAL411EQUALReactome Database ID Release 71927868Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=927868ReactomeR-HSA-9278681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-927868.1Reactome Database ID Release 71429842Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429842ReactomeR-HSA-4298421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429842.11PABPPABPC1Reactome DB_ID: 156803UniProt:P11940 PABPC1PABPC1PAB1PABP1PABPC2FUNCTION Binds the poly(A) tail of mRNA, including that of its own transcript, and regulates processes of mRNA metabolism such as pre-mRNA splicing and mRNA stability (PubMed:11051545, PubMed:17212783, PubMed:25480299). Its function in translational initiation regulation can either be enhanced by PAIP1 or repressed by PAIP2 (PubMed:11051545, PubMed:20573744). Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo. Involved in translationally coupled mRNA turnover (PubMed:11051545). Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain (PubMed:11051545). Involved in regulation of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons; for the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed (PubMed:18447585). By binding to long poly(A) tails, may protect them from uridylation by ZCCHC6/ZCCHC11 and hence contribute to mRNA stability (PubMed:25480299).FUNCTION (Microbial infection) Positively regulates the replication of dengue virus (DENV).SUBUNIT May interact with SETX (PubMed:21700224). May form homodimers. Component of a multisubunit autoregulatory ribonucleoprotein complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1 (PubMed:16356927). Directly interacts with IGF2BP1. Part of a complex associated with the FOS mCRD domain and consisting of HNRPD, SYNCRIP, PAIP1 and CSDE1/UNR (PubMed:11051545). Interacts with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1 and PAIP2 (PubMed:9548260, PubMed:11172725, PubMed:11438674, PubMed:11997512, PubMed:11287632, PubMed:20096703). Interacts with PAIP1 with a 1:1 stoichiometry and with PAIP2 with a 1:2 stoichiometry. The interaction with CSDE1 is direct and RNA-independent. Found in a mRNP complex with YBX2 (By similarity). Interacts with TENT2/GLD2 (By similarity). Identified in the spliceosome C complex (PubMed:11991638). Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with NFX1 (PubMed:17267499). Interacts with PIWIL1 (By similarity). Interacts with AGO1, AGO2, GSPT1 and GSPT2 (PubMed:17932509, PubMed:18447585, Ref.52). Interacts with LARP4B (Ref.54). Interacts (via the second and third RRM domains and the C-terminus) with PAIP2B (via central acidic portion and C-terminus) (PubMed:16804161, PubMed:11287632). Interacts with LARP1 (PubMed:20430826, PubMed:24532714, PubMed:25940091). Interacts with SHFL (PubMed:26735137). Found in a complex with SHFL and LARP1 (PubMed:26735137). Interacts with LARP4 (PubMed:21098120). Interacts with ZFC3H1 in a RNase-sensitive manner (PubMed:27871484). Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (PubMed:23125361). Interacts with TENT5C; the interaction has no effect on TENT5C poly(A) polymerase function (PubMed:28931820). Interacts with G3BP1 and G3BP2 (PubMed:23279204).SUBUNIT (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL69.TISSUE SPECIFICITY Ubiquitous.DOMAIN The RNA-binding domains RRM1 and RRM2 and the C-terminus (last 138 amino acids) regions interact with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1, respectively.DOMAIN The RNA-binding domains RRM2 and RRM3 and the C-terminus (last 138 amino acids) regions interact with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP2, respectively.PTM Phosphorylated by MAPKAPK2.PTM Methylated by CARM1. Arg-493 is dimethylated, probably to asymmetric dimethylarginine.MISCELLANEOUS Many viruses shutoff host mRNA translational machinery by inhibiting cellular PABPC1 activity using different mechanisms. Picornaviruses, caliciviruses or lentiviruses encode proteases that cleave PABPC1 at several defined sites in the proline-rich linker region between RRMs and the C-terminal domain. Rotaviruses, gammherpesviruses and bunyamwera virus relocalize PABPC1 from the cytoplasm to the nucleus thus altering its function. Many of these viruses translate their mRNA in a PABPC1-independent manner and are unaffected by host PABPC1 inhibition.SIMILARITY Belongs to the polyadenylate-binding protein type-1 family.CAUTION Was termed (Ref.5) polyadenylate binding protein II.UniProtP119401EQUAL636EQUALReactome Database ID Release 71156803Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=156803ReactomeR-HSA-1568031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-156803.11mature mRNA (eukaryotic, capped and partially deadenylated)Reactome DB_ID: 429909Reactome Database ID Release 71429909Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429909ReactomeR-ALL-4299091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-429909.11EIF4BeIF4BeIF-4Beukaryotic translation initiation factor 4BEukaryotic translation initiation factor 4BReactome DB_ID: 72589UniProt:P23588 EIF4BEIF4BFUNCTION Required for the binding of mRNA to ribosomes. Functions in close association with EIF4-F and EIF4-A. Binds near the 5'-terminal cap of mRNA in presence of EIF-4F and ATP. Promotes the ATPase activity and the ATP-dependent RNA unwinding activity of both EIF4-A and EIF4-F.SUBUNIT Self-associates and interacts with EIF3 p170 subunit.PTM Phosphorylated at Ser-422 by RPS6KA1 and RPS6KB1; phosphorylation enhances the affinity of EIF4B for the EIF3 complex.UniProtP235881EQUAL611EQUALReactome Database ID Release 7172589Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72589ReactomeR-HSA-725891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-72589.11Reactome Database ID Release 71429989Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=429989ReactomeR-HSA-4299891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-429989.1Uridylated partially Deadenylated mRNA ComplexReactome DB_ID: 896005911111Uridylated mRNAReactome DB_ID: 896005611Reactome Database ID Release 718960056Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8960056ReactomeR-ALL-89600561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-8960056.111Reactome Database ID Release 718960059Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8960059ReactomeR-HSA-89600591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8960059.1ACTIVATIONConverted from EntitySet in ReactomeZCCHC6, ZCCHC11Reactome DB_ID: 8941311TUT7ZCCHC6Terminal uridylyltransferase 7TUT7_HUMANReactome DB_ID: 8941313UniProt:Q5VYS8 TUT7TUT7ZCCHC6HS2KIAA1711FUNCTION Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:19703396, PubMed:25480299). Essential for both oocyte maturation and fertility. Through 3' terminal uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by eliminating transcripts during oocyte growth (By similarity). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets (PubMed:25480299). Also functions as an integral regulator of microRNA biogenesiS using 3 different uridylation mechanisms (PubMed:25979828). Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7). Uridylated pre-let-7 RNA is not processed by Dicer and undergo degradation. Pre-let-7 uridylation is strongly enhanced in the presence of LIN28A (PubMed:22898984). In the absence of LIN28A, TUT7 and TUT4 monouridylate group II pre-miRNAs, which includes most of pre-let7 members, that shapes an optimal 3' end overhang for efficient processing (PubMed:25979828, PubMed:28671666). Add oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-functional pre-miRNA species (PubMed:25979828). Does not play a role in replication-dependent histone mRNA degradation (PubMed:18172165). Due to functional redundancy between TUT4 and TUT7, the identification of the specific role of each of these proteins is difficult (PubMed:25979828, PubMed:25480299, PubMed:19703396, PubMed:22898984, PubMed:18172165, PubMed:28671666). TUT4 and TUT7 restrict retrotransposition of long interspersed element-1 (LINE-1) in cooperation with MOV10 counteracting the RNA chaperonne activity of L1RE1. TUT7 uridylates LINE-1 mRNAs in the cytoplasm which inhibits initiation of reverse transcription once in the nucleus, whereas uridylation by TUT4 destabilizes mRNAs in cytoplasmic ribonucleoprotein granules (PubMed:30122351).SUBUNIT Interacts with MOV10; the interaction is RNA-dependent.DOMAIN Utilizes two multidomain functional modules during the switch from monouridylation to oligouridylation. The catalytic module (containing the 3 CCHC-type Zinc finger domains) is essential for both activites while the Lin28-interacting module (LIM) at the N-termail part is indispensable for oligouridylation.SIMILARITY Belongs to the DNA polymerase type-B-like family.UniProtQ5VYS81EQUAL1495EQUALReactome Database ID Release 718941313Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941313ReactomeR-HSA-89413131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8941313.1ZCCHC11Terminal uridylyltransferase 4TUT4_HUMANReactome DB_ID: 8941307UniProt:Q5TAX3 TUT4TUT4ZCCHC11KIAA0191FUNCTION Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:25480299, PubMed:31036859). Essential for both oocyte maturation and fertility. Through 3' terminal uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by eliminating transcripts during oocyte growth (By similarity). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets. Also functions as an integral regulator of microRNA biogenesis using 3 different uridylation mechanisms (PubMed:25979828). Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7), miR107, miR-143 and miR-200c. Uridylated miRNAs are not processed by Dicer and undergo degradation. Degradation of pre-let-7 contributes to the maintenance of embryonic stem (ES) cell pluripotency (By similarity). Also catalyzes the 3' uridylation of miR-26A, a miRNA that targets IL6 transcript. This abrogates the silencing of IL6 transcript, hence promoting cytokine expression (PubMed:19703396). In the absence of LIN28A, TUT7 and TUT4 monouridylate group II pre-miRNAs, which includes most of pre-let7 members, that shapes an optimal 3' end overhang for efficient processing (PubMed:25979828). Adds oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-functional pre-miRNA species (PubMed:25979828). May also suppress Toll-like receptor-induced NF-kappa-B activation via binding to T2BP (PubMed:16643855). Does not play a role in replication-dependent histone mRNA degradation (PubMed:18172165). Due to functional redundancy between TUT4 and TUT7, the identification of the specific role of each of these proteins is difficult (PubMed:25979828, PubMed:25480299, PubMed:16643855, PubMed:19703396, PubMed:18172165) (By similarity). TUT4 and TUT7 restrict retrotransposition of long interspersed element-1 (LINE-1) in cooperation with MOV10 counteracting the RNA chaperonne activity of L1RE1. TUT7 uridylates LINE-1 mRNAs in the cytoplasm which inhibits initiation of reverse transcription once in the nucleus, whereas uridylation by TUT4 destabilizes mRNAs in cytoplasmic ribonucleoprotein granules (PubMed:30122351).SUBUNIT Interacts with LIN28A in the presence of pre-let-7 RNA (PubMed:19703396, PubMed:22118463, PubMed:31036859). Interacts with T2BP (PubMed:16643855). Interacts with MOV10; the interaction is RNA-dependent (PubMed:30122351).DOMAIN Utilizes two multidomain functional modules during the switch from monouridylation to oligouridylation. The catalytic module (containing the 3 CCHC-type Zinc finger domains) is essential for both activites while the Lin28-interacting module (LIM) at the N-termail part is indispensable for oligouridylation.SIMILARITY Belongs to the DNA polymerase type-B-like family.UniProtQ5TAX31EQUAL1644EQUALReactome Database ID Release 718941307Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941307ReactomeR-HSA-89413071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8941307.1Reactome Database ID Release 718941311Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941311ReactomeR-HSA-89413111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8941311.1GENE ONTOLOGYGO:0050265gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 718941303Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941303Reactome Database ID Release 718941312Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941312ReactomeR-HSA-89413121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8941312.127609902Pubmed2016TUT7 catalyzes the uridylation of the 3' end for rapid degradation of histone mRNALackey, Patrick EWelch, Joshua DMarzluff, William FRNA 22:1673-168815528436Pubmed2004Uridine addition after microRNA-directed cleavageShen, BinzhangGoodman, Howard MScience 306:99725171402Pubmed2014Emerging roles of RNA modification: m(6)A and U-tailLee, MihyeKim, BoseonKim, V NarryCell 158:980-727592415Pubmed2016Uridylation Earmarks mRNAs for Degradation… and MoreScheer, HélèneZuber, HélèneDe Almeida, CarolineGagliardi, DominiqueTrends Genet. 32:607-1924582499Pubmed2014TAIL-seq: genome-wide determination of poly(A) tail length and 3' end modificationsChang, HyeshikLim, JaechulHa, MinjuKim, V NarryMol. Cell 53:1044-5225223788Pubmed2014Selective microRNA uridylation by Zcchc6 (TUT7) and Zcchc11 (TUT4)Thornton, James EDu, PengJing, LiliSjekloca, LjiljanaLin, ShuibinGrossi, ElenaSliz, PiotrZon, Leonard IGregory, Richard INucleic Acids Res. 42:11777-9118172165Pubmed2008Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'Mullen, Thomas EMarzluff, William FGenes Dev. 22:50-6526078976Pubmed2015Polyuridylation in Eukaryotes: A 3'-End Modification Regulating RNA LifeMunoz-Tello, PaolaRajappa, LionalCoquille, SandrineThore, StéphaneBiomed Res Int 2015:96812721051505Pubmed2011The human cytoplasmic RNA terminal U-transferase ZCCHC11 targets histone mRNAs for degradationSchmidt, Marie-JoëlleWest, StevenNorbury, Chris JRNA 17:39-4423202588Pubmed2013Eri1 degrades the stem-loop of oligouridylated histone mRNAs to induce replication-dependent decayHoefig, Kai PRath, NicolaHeinz, Gitta AWolf, ChristineDameris, JasminSchepers, AloysKremmer, EAnsel, K MarkHeissmeyer, VigoNat. Struct. Mol. Biol. 20:73-8125027649Pubmed2014Regulation of microRNA biogenesisHa, MinjuKim, V NarryNat. Rev. Mol. Cell Biol. 15:509-2423385389Pubmed2013RNA decay via 3' uridylationScott, Daniel DNorbury, Chris JBiochim. Biophys. Acta 1829:654-6524656133Pubmed2014Deep sequencing shows multiple oligouridylations are required for 3' to 5' degradation of histone mRNAs on polyribosomesSlevin, Michael KMeaux, StacieWelch, Joshua DBigler, RebeccaMiliani de Marval, Paula LSu, WeiRhoads, Robert EPrins, Jan FMarzluff, William FMol. Cell 53:1020-3025480299Pubmed2014Uridylation by TUT4 and TUT7 marks mRNA for degradationLim, JaechulHa, MinjuChang, HyeshikKwon, S ChulSimanshu, Dhirendra KPatel, Dinshaw JKim, V NarryCell 159:1365-7623063654Pubmed2012Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAsHeo, InhaHa, MinjuLim, JaechulYoon, MJPark, Jong-EunKwon, S ChulChang, HyeshikKim, V NarryCell 151:521-32