来自韩国国立首尔大学的V. Narry Kim实验室发现Group II let-7 MicroRNAs生物合成过程中pre-microRNA的单尿苷化是重要步骤,本篇文章刊登在最新一期《CELL》杂志上。

-2012年10月26日《细胞》


中文翻译


【题目】Group II let-7 MicroRNAs生物合成过程中pre-microRNA的单尿苷化

【译文】RNase III Drosha通过切割一个前体miRNA转录物并释放出一个具有2 核苷酸3`突出端的pre-miRNA来使得microRNA(miRNA)成熟。Dicer识别2核苷酸 的3`突出端来选择性加工pre-miRNAs。我们发现不同于原核生物pre-miRNAs (group I),group II pre-miRNAs需要Drosha加工出一个较短的3`突出端(1 nt),因此需要Drosha加工的3`端单尿苷化。大部分的let-7和 miR-105属于group II。我们发现TUT7/ZCCHC6,TUT4/ZCCHC11和TUT2/PAPD4/GLD2作为末端尿苷转移酶负责pre-miRNA的单尿苷化。TUTs特异性的作用于带有1 核苷酸3`突出端的dsRNAs,形成2核苷酸的3`突出端。敲除TUTs会降低let-7的水平且破坏let-7的功能。尽管在胚胎干细胞中let-7的抑制因子Lin28可诱导抑制性多尿苷化,但缺少Lin8的体细胞仍然会发生单尿苷化从而促进let-7的生物合成。我们的研究反应了尿苷酸功能的双重性并且证明了TUT7/4/2参与miRNA生物合成途径。

英文原稿


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

[Authors]Inha Heo, Minju Ha, Jaechul Lim, Mi-Jeong Yoon, Jong-Eun Park, S. Chul Kwon, Hyeshik Chang, V. Narry Kim

[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.

原文地址

http://www.cell.com/abstract/S0092-8674(12)01129-4

 

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