title: Genome-wide studies reveal that Lin28 enhances the translation of genes important for growth and survival of human embryonic stem cells.
abstract: Lin28 inhibits the expression of let-7 microRNAs but also exhibits let-7-independent functions. Using immunoprecipitation and deep sequencing, we show here that Lin28 preferentially associates with a small subset of cellular mRNAs. Of particular interest are those for ribosomal proteins and metabolic enzymes, the expression levels of which are known to be coupled to cell growth and survival. Polysome profiling and reporter analyses suggest that Lin28 stimulates the translation of many or most of these targets. Moreover, Lin28-responsive elements were found within the coding regions of all target genes tested. Finally, a mutant Lin28 that still binds RNA but fails to interact with RNA helicase A (RHA), acts as a dominant-negative inhibitor of Lin28-dependent stimulation of translation. We suggest that Lin28, working in concert with RHA, enhances the translation of genes important for the growth and survival of human embryonic stem cells.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Shuping
authors.initials: S
authors.lastname: Peng
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chen
authors.forename: Xin-Xiang
authors.initials: XX
authors.lastname: Lei
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Haifan
authors.initials: H
authors.lastname: Lin
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Carmichael
authors.forename: Yingqun
authors.initials: Y
authors.lastname: Huang
mesh_terms: D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D050437:Genes, Developmental / Q000235:genetics; D056726:Genetic Association Studies; D015894:Genome, Human; D006801:Humans; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C000715187:Lin28A protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins