Genome-Wide Studies Reveal That Lin28 Enhances the Translation of Genes Important for Growth and Survival of Human Embryonic Stem Cells

被引：157

作者：

Peng, Shuping ^{[1
,2
]}

Chen, Ling-Ling ^{[3
]}

Lei, Xin-Xiang ^{[1
,4
]}

Yang, Li ^{[3
]}

Lin, Haifan ^{[2
]}

Carmichael, Gordon G. ^{[3
]}

Huang, Yingqun ^{[1
,2
]}

机构：

[1] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, New Haven, CT 06511 USA

[2] Yale Univ, Sch Med, Yale Stem Cell Ctr, New Haven, CT USA

[3] Univ Connecticut, Ctr Hlth, Univ Connecticut Stem Cell Inst, Dept Genet & Dev Biol, Farmington, CT USA

[4] Wenzhou Univ, Dept Chem, Wenzhou, Zhejiang, Peoples R China

来源：

STEM CELLS | 2011年 / 29卷 / 03期

关键词：

Lin28; Stem cell; Translation; Growth; Metabolism; LET-7; MICRORNA; MESSENGER-RNA; PROTEIN; LIN-28; BINDING; BIOGENESIS; EXPRESSION; MDM2;

D O I：

10.1002/stem.591

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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

引用

页码：496 / 504

页数：9

共 37 条

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