Identification of LIN28B-bound mRNAs reveals features of target recognition and regulation

被引：67

作者：

Graf, Robin ^{[1
]}

Munschauer, Mathias ^{[1
]}

Mastrobuoni, Guido ^{[2
]}

Mayr, Florian ^{[1
]}

Heinemann, Udo ^{[1
]}

Kempa, Stefan ^{[2
]}

Rajewsky, Nikolaus ^{[1
]}

Landthaler, Markus ^{[1
]}

机构：

[1] Max Delbruck Ctr Mol Med, Berlin, Germany

[2] Max Delbruck Ctr Mol Med, Integrat Prote & Metabol Platform, Berlin, Germany

来源：

RNA BIOLOGY | 2013年 / 10卷 / 07期

关键词：

BINDING-PROTEIN; PROMOTES TRANSFORMATION; MICRORNA BIOGENESIS; LIN28; EXPRESSION; TRANSLATION; LIN-28; DOMAIN; AUTOREGULATION; TRANSCRIPTION;

D O I：

10.4161/rna.25194

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The conserved human LIN28 RNA-binding proteins function in development, maintenance of pluripotency and oncogenesis. We used PAR-CLIP and a newly developed variant of this method, iDo-PAR-CLIP, to identify LIN28B targets as well as sites bound by the individual RNA-binding domains of LIN28B in the human transcriptome at nucleotide resolution. The position of target binding sites reflected the known structural relative orientation of individual LIN28Bbinding domains, validating iDo-PAR-CLIP. Our data suggest that LIN28B directly interacts with most expressed mRNAs and members of the let-7 microRNA family. The Lin28-binding motif detected in pre-let-7 was enriched in mRNA sequences bound by LIN28B. Upon LIN28B knockdown, cell proliferation and the cell cycle were strongly impaired. Quantitative shotgun proteomics of LIN28B depleted cells revealed significant reduction of protein synthesis from its RNA targets. Computational analyses provided evidence that the strength of protein synthesis reduction correlated with the location of LIN28B binding sites within target transcripts. © 2013 Landes Bioscience.

引用

页码：1146 / 1159

页数：14

共 70 条

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