Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510, USA.
Nucleic Acids Res. 2011 May;39(9):3724-34. doi: 10.1093/nar/gkq1350. Epub 2011 Jan 18.
The stem cell protein Lin28 functions to inhibit the biogenesis of a group of miRNAs but also stimulates the expression of a subset of mRNAs at the post-transcriptional level, the underlying mechanism of which is not yet understood. Here we report the characterization of the molecular interplay between Lin28 and RNA helicase A (RHA) known to play an important role in remodeling ribonucleoprotein particles during translation. We show that reducing Lin28 expression results in decreased RHA association with polysomes while increasing Lin28 expression leads to elevated RHA association. Further, the carboxyl terminus of Lin28 is necessary for interaction with both the amino and carboxyl termini of RHA. Importantly, a carboxyl terminal deletion mutant of Lin28 that retains RNA-binding activity fails to interact with RHA and exhibits dominant-negative effects on Lin28-dependent stimulation of translation. Taken together, these results lead us to suggest that Lin28 may stimulate translation by actively recruiting RHA to polysomes.
干细胞蛋白 Lin28 可抑制一组 miRNA 的生物发生，但也可在后转录水平刺激一组 mRNA 的表达，其潜在机制尚不清楚。在这里，我们报告了 Lin28 与 RNA 解旋酶 A（RHA）之间分子相互作用的特征，RHA 在翻译过程中重塑核糖核蛋白颗粒中起着重要作用。我们表明，降低 Lin28 的表达会导致 RHA 与多核糖体的结合减少，而增加 Lin28 的表达会导致 RHA 结合增加。此外，Lin28 的羧基末端对于与 RHA 的氨基和羧基末端的相互作用都是必需的。重要的是，Lin28 的保留 RNA 结合活性的羧基末端缺失突变体不能与 RHA 相互作用，并对 Lin28 依赖性翻译刺激表现出显性负效应。总之，这些结果表明 Lin28 可能通过主动将 RHA 募集到多核糖体上来刺激翻译。
