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

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Title
LIN28A Is a Suppressor of ER-Associated Translation in Embryonic Stem Cells
Author(s)
Jun Cho; Hyeshik Chang; S. Chul Kwon; Baekgyu Kim; Yoosik Kim; Junho Choe; Minju Ha; Yoon Ki Kim; V. Narry Kim
Publication Date
2012-11
Journal
CELL, v.151, no.4, pp.765 - 777
Publisher
CELL PRESS
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.
URI
https://pr.ibs.re.kr/handle/8788114/1422
ISSN
0092-8674
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
Files in This Item:
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