LIN28A Is a Suppressor of ER-Associated Translation in Embryonic Stem Cells

被引：196

作者：

Cho, Jun ^{[1
,2
]}

Chang, Hyeshik ^{[1
,2
]}

Kwon, S. Chul ^{[1
,2
]}

Kim, Baekgyu ^{[1
,2
]}

Kim, Yoosik ^{[1
,2
]}

Choe, Junho ^{[3
]}

Ha, Minju ^{[1
,2
]}

Kim, Yoon Ki ^{[3
]}

Kim, V. Narry ^{[1
,2
]}

机构：

[1] Seoul Natl Univ, Inst Basic Sci, Seoul 151742, South Korea

[2] Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea

[3] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea

来源：

CELL | 2012年 / 151卷 / 04期

基金：

新加坡国家研究基金会;

关键词：

MESSENGER-RNA; NUCLEOTIDE RESOLUTION; MICRORNA BIOGENESIS; LET-7; MICRORNA; BINDING-SITES; CROSS-LINKING; IN-VIVO; CLIP; LIN-28; PROTEINS;

D O I：

10.1016/j.cell.2012.10.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

LIN28 plays a critical role in developmental transition, glucose metabolism, and tumorigenesis. At the molecular level, LIN28 is known to repress maturation of let-7 microRNAs and enhance translation of certain mRNAs. In this study, we obtain a genome-wide view of the molecular function of LIN28A in mouse embryonic stem cells by carrying out RNA crosslinking-immunoprecipitation-sequencing (CLIP-seq) and ribosome footprinting. We find that, in addition to let-7 precursors, LIN28A binds to a large number of spliced mRNAs. LIN28A recognizes AAGNNG, AAGNG, and less frequently UGUG, which are located in the terminal loop of a small hairpin. LIN28A is localized to the periendo-plasmic reticulum (ER) area and inhibits translation of mRNAs that are destined for the ER, reducing the synthesis of transmembrane proteins, ER or Golgi lumen proteins, and secretory proteins. Our study suggests a selective regulatory mechanism for ER-associated translation and reveals an unexpected role of LIN28A as a global suppressor of genes in the secretory pathway.

引用

页码：765 / 777

页数：13

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