Structural highlights
Function
[TUT7_HUMAN] 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). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets (PubMed:25480299). Also 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). Due to functional redundancy between ZCCHC6 and ZCCHC11, the identification of the specific role of each of these proteins is difficult.[1] [2] [3]
Publication Abstract from PubMed
The uridyl transferases TUT4 and TUT7 (collectively called TUT4(7)) switch between two modes of activity, either promoting expression of let-7 microRNA (monoU) or marking it for degradation (oligoU). Lin28 modulates the switch via recruitment of TUT4(7) to the precursor pre-let-7 in stem cells and human cancers. We found that TUT4(7) utilize two multidomain functional modules during the switch from monoU to oligoU. The catalytic module (CM) is essential for both activities, while the Lin28-interacting module (LIM) is indispensable for oligoU. A TUT7 CM structure trapped in the monoU activity staterevealed a duplex-RNA-binding pocket that orients group II pre-let-7 hairpins to favor monoU addition. Conversely, the switch to oligoU requires the ZK domain of Lin28 to drive the formation of a stable ternary complex between pre-let-7 and the inactive LIM. Finally, ZK2 of TUT4(7) aids oligoU addition by engaging the growing oligoU tail through uracil-specific interactions.
Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis.,Faehnle CR, Walleshauser J, Joshua-Tor L Nat Struct Mol Biol. 2017 Aug;24(8):658-665. doi: 10.1038/nsmb.3428. Epub 2017, Jul 3. PMID:28671666[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ Thornton JE, Chang HM, Piskounova E, Gregory RI. Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7). RNA. 2012 Oct;18(10):1875-85. doi: 10.1261/rna.034538.112. Epub 2012 Aug 16. PMID:22898984 doi:http://dx.doi.org/10.1261/rna.034538.112
- ↑ 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
- ↑ Faehnle CR, Walleshauser J, Joshua-Tor L. Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis. Nat Struct Mol Biol. 2017 Aug;24(8):658-665. doi: 10.1038/nsmb.3428. Epub 2017, Jul 3. PMID:28671666 doi:http://dx.doi.org/10.1038/nsmb.3428
