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LIN28A is a suppressor of ER-associated translation in embryonic stem cells

Cited 152 time in Web of Science Cited 149 time in Scopus
Authors
Cho, Jun; Chang, Hyeshik; Kwon, S. Chul; Kim, Baekgyu; Kim, Yoosik; Choe, Junho; Ha, Minju; Kim, Yoon Ki; Kim, V. Narry
Issue Date
2012-11
Citation
Cell, Vol.151 No.4, pp.765-777
Abstract
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.
ISSN
0092-8674
URI
https://hdl.handle.net/10371/171921
DOI
https://doi.org/10.1016/j.cell.2012.10.019
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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