Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7)
Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7)
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DOI：
10.1261/rna.034538.112
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发表时间：
2012-10-01
期刊：
影响因子：
4.5
通讯作者：
Gregory, Richard I.
中科院分区：
文献类型：
--
作者：
Thornton, James E.;Chang, Hao-Ming;Gregory, Richard I.
多能性因子Lin 28募集3'末端尿苷酰转移酶（TUTase）以选择性地阻断未分化细胞中的let-7 microRNA生物合成。Zcchc 11（TUTase 4/TUT 4）先前被鉴定为负责Lin 28介导的pre-let-7尿苷酸化和let-7表达控制的酶。在这里，我们研究这种相互作用的蛋白质和RNA的决定因素。生化解剖和重建分析揭示了TUTase结构域对于Lin 28增强的pre-let-7尿苷化是必要和足够的。一个单一的C2 H2型锌指结构域的Zcchc 11被认为是负责与Lin 28的功能相互作用。我们确定Zcchc 6（TUTase 7）作为一种替代TUTase的功能与林28在体外，因此，我们发现Zcchc 11和Zcchc 6冗余控制让-7在胚胎干细胞的生物发生。我们的研究表明，Lin 28使用两种不同的TUTases来控制let-7的表达，对干细胞生物学和癌症具有重要意义。
The pluripotency factor Lin28 recruits a 3' terminal uridylyl transferase (TUTase) to selectively block let-7 microRNA biogenesis in undifferentiated cells. Zcchc11 (TUTase4/TUT4) was previously identified as an enzyme responsible for Lin28-mediated pre-let-7 uridylation and control of let-7 expression. Here we investigate the protein and RNA determinants for this interaction. Biochemical dissection and reconstitution assays reveal the TUTase domains necessary and sufficient for Lin28-enhanced pre-let-7 uridylation. A single C2H2-type zinc finger domain of Zcchc11 was found to be responsible for the functional interaction with Lin28. We identify Zcchc6 (TUTase7) as an alternative TUTase that functions with Lin28 in vitro, and accordingly, we find Zcchc11 and Zcchc6 redundantly control let-7 biogenesis in embryonic stem cells. Our study indicates that Lin28 uses two different TUTases to control let-7 expression and has important implications for stem cell biology as well as cancer.