Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/81065
Type: Artigo de periódico
Title: LIN28 Binds Messenger RNAs at GGAGA Motifs and Regulates Splicing Factor Abundance
Author: Wilbert, ML
Huelga, SC
Kapeli, K
Stark, TJ
Liang, TY
Chen, SX
Yan, BY
Nathanson, JL
Hutt, KR
Lovci, MT
Kazan, H
Vu, AQ
Massirer, KB
Morris, Q
Hoon, S
Yeo, GW
Abstract: LIN28 is a conserved RNA-binding protein implicated in pluripotency, reprogramming, and oncogenesis. It was previously shown to act primarily by blocking let-7 microRNA (miRNA) biogenesis, but here we elucidate distinct roles of LIN28 regulation via its direct messenger RNA (mRNA) targets. Through crosslinking and immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells and somatic cells expressing exogenous LIN28, we have defined discrete LIN28-binding sites in a quarter of human transcripts. These sites revealed that LIN28 binds to GGAGA sequences enriched within loop structures in mRNAs, reminiscent of its interaction with let-7 miRNA precursors. Among LIN28 mRNA targets, we found evidence for LIN28 autoregulation and also direct but differing effects on the protein abundance of splicing regulators in somatic and pluripotent stem cells. Splicing-sensitive microarrays demonstrated that exogenous LIN28 expression causes widespread downstream alternative splicing changes. These findings identify important regulatory functions of LIN28 via direct mRNA interactions.
Country: EUA
Editor: Cell Press
Rights: fechado
Identifier DOI: 10.1016/j.molcel.2012.08.004
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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