Lin28 通过 TUTases Zcchc11（TUT4）和 Zcchc6（TUT7）调控 let-7 微 RNA 的表达。
Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7).
机构信息
Stem Cell Program, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
出版信息
RNA. 2012 Oct;18(10):1875-85. doi: 10.1261/rna.034538.112. Epub 2012 Aug 16.
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.
多能性因子 Lin28 招募 3' 末端尿嘧啶转移酶 (TUTase) 来选择性地阻断未分化细胞中 let-7 microRNA 的生物发生。Zcchc11（TUTase4/TUT4）先前被鉴定为负责 Lin28 介导的 pre-let-7 尿嘧啶化和 let-7 表达调控的酶。在这里，我们研究了这种相互作用的蛋白质和 RNA 决定因素。生化分析和重组测定揭示了 Lin28 增强 pre-let-7 尿嘧啶化所必需和充分的 TUTase 结构域。发现 Zcchc11 的单个 C2H2 型锌指结构域负责与 Lin28 的功能相互作用。我们鉴定 Zcchc6（TUTase7）为体外与 Lin28 功能相关的替代 TUTase，因此，我们发现 Zcchc11 和 Zcchc6 在胚胎干细胞中冗余地控制 let-7 的生物发生。我们的研究表明，Lin28 使用两种不同的 TUTase 来控制 let-7 的表达，这对干细胞生物学和癌症都有重要意义。
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