TY - JOUR
T1 - LIN28A is a suppressor of ER-associated translation in embryonic stem cells
AU - Cho, Jun
AU - Chang, Hyeshik
AU - Kwon, S. Chul
AU - Kim, Baekgyu
AU - Kim, Yoosik
AU - Choe, Junho
AU - Ha, Minju
AU - Kim, Yoon Ki
AU - Kim, V. Narry
N1 - Funding Information:
We are grateful to Huili Guo for advice on ribosome profiling and Daehyun Baek for critical comments on the manuscript. We also thank Ahyoung Cho and Yun Cheng Chang for technical help and members of our laboratory for discussion. This work was supported by the Research Center Program (EM1202) of IBS (Institute for Basic Science); the BK21 Research Fellowships (J.C., H.C., S.C.K., and B.K.) from the Ministry of Education, Science and Technology of Korea; the TJ Park Postdoctoral Fellowship (Y.K.); and the National Honor Scientist Program (20100020415) through the National Research Foundation of Korea (NRF).
PY - 2012/11/9
Y1 - 2012/11/9
N2 - 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 periendoplasmic 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.
AB - 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 periendoplasmic 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.
UR - http://www.scopus.com/inward/record.url?scp=84869086143&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2012.10.019
DO - 10.1016/j.cell.2012.10.019
M3 - Article
C2 - 23102813
AN - SCOPUS:84869086143
SN - 0092-8674
VL - 151
SP - 765
EP - 777
JO - Cell
JF - Cell
IS - 4
ER -