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Mono-Uridylation of Pre-MicroRNA as a Key Step in the Biogenesis of Group II let-7 MicroRNAs

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Title
Mono-Uridylation of Pre-MicroRNA as a Key Step in the Biogenesis of Group II let-7 MicroRNAs
Author(s)
Inha Heo; Minju Ha; Jaechul Lim; Mi-Jeong Yoon; Jong-Eun Park; S. Chul Kwon; Hyeshik Chang; V. Narry Kim
Publication Date
2012-10
Journal
CELL, v.151, no.3, pp.521 - 532
Publisher
CELL PRESS
Abstract
RNase III Drosha initiates microRNA (miRNA) maturation by cleaving a primary miRNA transcript and releasing a pre-miRNA with a 2 nt 3` overhang. Dicer recognizes the 2 nt 3` overhang structure to selectively process pre-miRNAs. Here, we find that, unlike prototypic pre-miRNAs #group I#, group II pre-miRNAs acquire a shorter #1 nt# 3` overhang from Drosha processing and therefore require a 3`-end mono-uridylation for Dicer processing. The majority of let-7 and miR-105 belong to group II. We identify TUT7/ZCCHC6, TUT4/ZCCHC11, and TUT2/PAPD4/GLD2 as the terminal uridylyl transferases responsible for pre-miRNA mono-uridylation. The TUTs act specifically on dsRNAs with a 1 nt 3` overhang, thereby creating a 2 nt 3` overhang. Depletion of TUTs reduces let-7 levels and disrupts let-7 function. Although the let-7 suppressor, Lin28, induces inhibitory oligo-uridylation in embryonic stem cells, mono-uridylation occurs in somatic cells lacking Lin28 to promote let-7 biogenesis. Our study reveals functional duality of uridylation and introduces TUT7/4/2 as components of the miRNA biogenesis pathway.
URI
https://pr.ibs.re.kr/handle/8788114/1424
ISSN
0092-8674
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
Files in This Item:
2012-10-26-Cell-Mono_Uridylation.pdfDownload

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