Yale Stem Cell Center, PO Box 208073, New Haven, CT 06520, USA.
Nucleic Acids Res. 2010 Mar;38(4):1240-8. doi: 10.1093/nar/gkp1071. Epub 2009 Dec 4.
Lin28 acts as a repressor of microRNA processing and as a post-transcriptional regulatory factor for a subset of mRNAs. Here we report that in human embryonic stem cells Lin28 facilitates the expression of the pivotal pluripotency factor Oct4 at the post-transcriptional level. We provide evidence that Lin28 binds Oct4 mRNA directly through high affinity sites within its coding region and that an interaction between Lin28 and RNA helicase A (RHA) may play a part in the observed regulation. We further demonstrate that decreasing RHA levels impairs Lin28-dependent stimulation of translation in a reporter system. Taken together with previous studies showing that RHA is required for efficient translation of a specific class of mRNAs, these findings suggest a novel mechanism by which Lin28 may affect target mRNA expression and represent the first evidence of post-transcriptional regulation of Oct4 expression by Lin28 in human embryonic stem cells.
Lin28 作为 microRNA 加工的抑制剂和一组 mRNA 的转录后调控因子发挥作用。在这里，我们报告在人类胚胎干细胞中，Lin28 在转录后水平促进关键多能性因子 Oct4 的表达。我们提供的证据表明，Lin28 通过其编码区内的高亲和力结合位点直接结合 Oct4 mRNA，Lin28 和 RNA 解旋酶 A（RHA）之间的相互作用可能在观察到的调节中发挥作用。我们进一步证明，降低 RHA 水平会损害报告系统中 Lin28 依赖性翻译的刺激。与先前表明 RHA 是特定一类 mRNA 高效翻译所必需的研究相结合，这些发现表明了 Lin28 可能影响靶 mRNA 表达的一种新机制，并代表了 Lin28 在人类胚胎干细胞中对 Oct4 表达进行转录后调控的第一个证据。
