Open AccessGenome‐Wide Studies Reveal That Lin28 Enhances the Translation of Genes Important for Growth and Survival of Human Embryonic Stem Cells
Author(s) -
Peng Shuping,
Chen LingLing,
Lei XinXiang,
Yang Li,
Lin Haifan,
Carmichael Gordon G.,
Huang Yingqun
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.591
Subject(s) - lin28 , biology , embryonic stem cell , microrna , gene , stem cell , polysome , microbiology and biotechnology , translation (biology) , rna , genetics , messenger rna , ribosome , induced pluripotent stem cell
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. S TEM C ELLS 2011;496–504