9w4s

Structural highlights

Function

TUT4_HUMAN Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (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. 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).[UniProtKB:B2RX14]^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Minoda Y, Saeki K, Aki D, Takaki H, Sanada T, Koga K, Kobayashi T, Takaesu G, Yoshimura A. A novel Zinc finger protein, ZCCHC11, interacts with TIFA and modulates TLR signaling. Biochem Biophys Res Commun. 2006 Jun 9;344(3):1023-30. Epub 2006 Apr 19. PMID:16643855 doi:http://dx.doi.org/S0006-291X(06)00811-4
2. ↑ Mullen TE, Marzluff WF. Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'. Genes Dev. 2008 Jan 1;22(1):50-65. doi: 10.1101/gad.1622708. PMID:18172165 doi:10.1101/gad.1622708
3. ↑ Heo I, Joo C, Kim YK, Ha M, Yoon MJ, Cho J, Yeom KH, Han J, Kim VN. TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell. 2009 Aug 21;138(4):696-708. doi: 10.1016/j.cell.2009.08.002. PMID:19703396 doi:http://dx.doi.org/10.1016/j.cell.2009.08.002
4. ↑ Lim J, Ha M, Chang H, Kwon SC, Simanshu DK, Patel DJ, Kim VN. Uridylation by TUT4 and TUT7 marks mRNA for degradation. Cell. 2014 Dec 4;159(6):1365-76. doi: 10.1016/j.cell.2014.10.055. PMID:25480299 doi:http://dx.doi.org/10.1016/j.cell.2014.10.055
5. ↑ Kim B, Ha M, Loeff L, Chang H, Simanshu DK, Li S, Fareh M, Patel DJ, Joo C, Kim VN. TUT7 controls the fate of precursor microRNAs by using three different uridylation mechanisms. EMBO J. 2015 Jul 2;34(13):1801-15. doi: 10.15252/embj.201590931. Epub 2015 May, 15. PMID:25979828 doi:http://dx.doi.org/10.15252/embj.201590931
6. ↑ Warkocki Z, Krawczyk PS, Adamska D, Bijata K, Garcia-Perez JL, Dziembowski A. Uridylation by TUT4/7 Restricts Retrotransposition of Human LINE-1s. Cell. 2018 Sep 6;174(6):1537-1548.e29. doi: 10.1016/j.cell.2018.07.022. Epub 2018, Aug 16. PMID:30122351 doi:http://dx.doi.org/10.1016/j.cell.2018.07.022