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

被引：252

作者：

Heo, Inha ^{[1
,2
]}

Ha, Minju ^{[1
,2
]}

Lim, Jaechul ^{[1
,2
]}

Yoon, Mi-Jeong ^{[2
]}

Park, Jong-Eun ^{[1
,2
]}

Kwon, S. Chul ^{[1
,2
]}

Chang, Hyeshik ^{[1
,2
]}

Kim, V. Narry ^{[1
,2
]}

机构：

[1] Seoul Natl Univ, Inst Basic Sci, Seoul 151742, South Korea

[2] Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea

来源：

CELL | 2012年 / 151卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

RNA-INTERFERENCE; C-ELEGANS; POLY(A) POLYMERASES; NUCLEAR EXPORT; MICROPROCESSOR COMPLEX; CAENORHABDITIS-ELEGANS; DROSHA-DGCR8; COMPLEX; MOLECULAR-BASIS; 3' ADENYLATION; MESSENGER-RNA;

D O I：

10.1016/j.cell.2012.09.022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：521 / 532

页数：12

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