Non-microRNA binding competitively inhibits LIN28 regulation

Cell Reports

卷:36

Emily C. Wheeler¹  Shashank Sathe²  Frederick E. Tan³  Gene W. Yeo³ 

[1] Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA;

[2] Stem Cell Program, University of California, San Diego, La Jolla, CA, USA;

[3] Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA;

关键词: RNA binding proteins;    post-transcriptional regulation;    microRNA;    non-miRNA;    ribosome occupancy;    competitive inhibition;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: RNA binding protein (RBP) expression is finite. For RBPs that are vastly outnumbered by their potential target sites, a simple competition for binding can set the magnitude of post-transcriptional control. Here, we show that LIN28, best known for its direct regulation of let-7 miRNA biogenesis, is also indirectly regulated by its widespread binding of non-miRNA transcripts. Approximately 99% of LIN28 binding sites are found on non-miRNA transcripts, like protein coding and ribosomal RNAs. These sites are bound specifically and strongly, but they do not appear to mediate direct post-transcriptional regulation. Instead, non-miRNA sites act to sequester LIN28 protein and effectively change its functional availability, thus impeding the regulation of let-7 in cells. Together, these data show that the binding properties of the transcriptome broadly influence the ability of an RBP to mediate changes in RNA metabolism and gene expression.

【 授权许可】

Unknown