Genome-Wide Studies Reveal That Lin28 Enhances the Translation of Genes Important for Growth and Survival of Human Embryonic Stem Cells
Genome-Wide Studies Reveal That Lin28 Enhances the Translation of Genes Important for Growth and Survival of Human Embryonic Stem Cells
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DOI：
10.1002/stem.591
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发表时间：
2011-03-01
期刊：
影响因子：
5.2
通讯作者：
Huang, Yingqun
中科院分区：
文献类型：
--
作者：
Peng, Shuping;Chen, Ling-Ling;Huang, Yingqun
Lin28抑制let-7 microrna的表达，但也表现出与let-7无关的功能。通过免疫沉淀和深度测序，我们发现Lin28优先与一小部分细胞mrna结合。特别令人感兴趣的是核糖体蛋白和代谢酶的表达水平，它们的表达水平已知与细胞生长和存活有关。多聚体分析和报告分析表明，Lin28刺激了许多或大部分这些靶标的翻译。此外，在所有测试的靶基因的编码区内都发现了lin28应答元件。最后，突变体Lin28仍然结合RNA，但不能与RNA解旋酶a （RHA）相互作用，作为Lin28依赖性翻译刺激的显性阴性抑制剂。我们认为，Lin28与RHA协同作用，增强了对人类胚胎干细胞生长和存活重要基因的翻译。干细胞2011；29:496 - 504
Lin28 inhibits the expression of let-7 microRNAs but also exhibits let-7-independent functions. Using immunoprecipitation and deep sequencing, we show here that Lin28 preferentially associates with a small subset of cellular mRNAs. Of particular interest are those for ribosomal proteins and metabolic enzymes, the expression levels of which are known to be coupled to cell growth and survival. Polysome profiling and reporter analyses suggest that Lin28 stimulates the translation of many or most of these targets. Moreover, Lin28-responsive elements were found within the coding regions of all target genes tested. Finally, a mutant Lin28 that still binds RNA but fails to interact with RNA helicase A (RHA), acts as a dominant-negative inhibitor of Lin28-dependent stimulation of translation. We suggest that Lin28, working in concert with RHA, enhances the translation of genes important for the growth and survival of human embryonic stem cells. STEM CELLS 2011;29:496-504