title: LIN28A is a suppressor of ER-associated translation in embryonic stem cells.
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 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.
authors.affiliation: Institute for Basic Science, Seoul National University, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Cho
authors.affiliation: Institute for Basic Science, Seoul National University, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Hyeshik
authors.initials: H
authors.lastname: Chang
authors.affiliation: Institute for Basic Science, Seoul National University, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: S Chul
authors.initials: SC
authors.lastname: Kwon
authors.affiliation: Institute for Basic Science, Seoul National University, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Baekgyu
authors.initials: B
authors.lastname: Kim
authors.affiliation: Institute for Basic Science, Seoul National University, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Yoosik
authors.initials: Y
authors.lastname: Kim
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
authors.forename: Junho
authors.initials: J
authors.lastname: Choe
authors.affiliation: Institute for Basic Science, Seoul National University, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Minju
authors.initials: M
authors.lastname: Ha
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Institute for Basic Science, Seoul National University, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea. Electronic address: narrykim@snu.ac.kr.
authors.forename: V Narry
authors.initials: VN
authors.lastname: Kim
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D047468:Immunoprecipitation / Q000379:methods; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D055571:Secretory Pathway; D017423:Sequence Analysis, RNA
chemical_list: C488352:Lin-28 protein, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C542687:mirnlet7 microRNA, mouse