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TUT4 in Concert with Lin28 Suppresses MicroRNA Biogenesis through Pre-MicroRNA Uridylation

Cited 546 time in Web of Science Cited 588 time in Scopus
Authors
Heo, Inha; Joo, Chirlmin; Kim, Young-Kook; Ha, Minju; Yoon, Mi-Jeong; Cho, Jun; Yeom, Kyu-Hyeon; Han, Jinju; Kim, V. Narry
Issue Date
2009-08
Citation
Cell, Vol.138 No.4, pp.696-708
Abstract
As key regulators in cellular functions, microRNAs (miRNAs) themselves need to be tightly controlled. Lin28, a pluripotency factor, was reported to downregulate let-7 miRNA by inducing uridylation of let-7 precursor (pre-let-7). But the enzyme responsible for the uridylation remained unknown. Here we identify a noncanonical poly (A) polymerase, TUTase4 (TUT4), as the uridylyl transferase for pre-let-7. Lin28 recruits TUT4 to pre-let-7 by recognizing a tetra-nucleotide sequence motif (GGAG) in the terminal loop. TUT4 in turn adds an oligouridine tail to the pre-let-7, which blocks Dicer processing. Other miRNAs with the same sequence motif (miR-107, -143, and -200c) are regulated through the same mechanism. Knockdown of TUT4 and Lin28 reduces the level of stem cell markers, suggesting that they are required for stem cell maintenance. This study uncovers the role of TUT4 and Lin28 as specific suppressors of miRNA biogenesis, which has implications for stem cell research and cancer biology.
ISSN
0092-8674
URI
https://hdl.handle.net/10371/171925
DOI
https://doi.org/10.1016/j.cell.2009.08.002
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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