title: TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation.
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.
authors.affiliation: Creative Research Center and School of Biological Sciences, Seoul National University, Seoul, Korea.
authors.forename: Inha
authors.initials: I
authors.lastname: Heo
authors.forename: Chirlmin
authors.initials: C
authors.lastname: Joo
authors.forename: Young-Kook
authors.initials: YK
authors.lastname: Kim
authors.forename: Minju
authors.initials: M
authors.lastname: Ha
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Yoon
authors.forename: Jun
authors.initials: J
authors.lastname: Cho
authors.forename: Kyu-Hyeon
authors.initials: KH
authors.lastname: Yeom
authors.forename: Jinju
authors.initials: J
authors.lastname: Han
authors.forename: V Narry
authors.initials: VN
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology*; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D011062:Polynucleotide Adenylyltransferase / Q000378:metabolism*; D014529:Uridine / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D011062:Polynucleotide Adenylyltransferase; D014529:Uridine