Non-microRNA binding competitively inhibits LIN28 regulation

Frederick E Tan; Shashank Sathe; Emily C Wheeler; Gene W Yeo

doi:10.1016/j.celrep.2021.109517

Non-microRNA binding competitively inhibits LIN28 regulation

Cell Rep. 2021 Aug 10;36(6):109517. doi: 10.1016/j.celrep.2021.109517.

Authors

Frederick E Tan¹, Shashank Sathe¹, Emily C Wheeler¹, Gene W Yeo²

Affiliations

¹ Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
² Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address: geneyeo@ucsd.edu.

Abstract

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.

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

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Binding Sites
Gene Expression Regulation*
HEK293 Cells
Humans
Mice
MicroRNAs / metabolism*
Mouse Embryonic Stem Cells / metabolism
Protein Binding
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism
Transcriptome / genetics

Substances

Lin28A protein, human
MicroRNAs
RNA-Binding Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding