YB-3 substitutes YB-1 in global mRNA binding

RNA Biol. 2020 Apr;17(4):487-499. doi: 10.1080/15476286.2019.1710050. Epub 2020 Jan 16.

Abstract

Y-box binding proteins are DNA- and RNA-binding proteins with an evolutionarily ancient and conserved cold shock domain. The Y-box binding protein 1 (YB-1) is the most studied due to its abundance in somatic cells. YB-1 is involved in a variety of cellular processes, including proliferation, differentiation and stress response. Here, using Ribo-Seq and RIP-Seq we confirm that YB-1 binds a wide range of mRNAs and globally acts as a translation inhibitor. Surprisingly, YBX1 knockout results in only minor alterations in the expression of other genes, mostly caused by changes in RNA abundance. But YB-3 mRNA is an exception: it is better translated in the absence of YB-1, thereby producing an increased amount of YB-3 and thus suggesting that its synthesis is under YB-1 negative control. We have shown that the set of mRNAs bound to YB-3 is strikingly similar to that of YB-1, and that the mRNA-binding by YB-3 is enhanced in the absence of YB-1, resulting in a similar global reduction of translation of bound mRNAs in YB-1-null cells. Thus, YB-3 acts as a substitute for YB-1 in mRNA binding and, probably, in global translational control.

Keywords: RIP-Seq; Ribo-Seq; YB-1; YB-3; YBX1; YBX3; translational control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation
  • Gene Knockout Techniques
  • HEK293 Cells
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Protein Biosynthesis
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism*
  • Ribosomes / genetics
  • Ribosomes / metabolism
  • Y-Box-Binding Protein 1 / genetics
  • Y-Box-Binding Protein 1 / metabolism*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • Heat-Shock Proteins
  • RNA, Messenger
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • YBX3 protein, human

Grants and funding

This work was supported by the Russian Science Foundation (#19-74-20129) [high-throughput sequencing experiments] and the Russian Foundation for Basic Research (#18-04-00595) [section ‘YB-1 controls YB-3 expression’]. Open access is funded by the Russian Science Foundation (#19-74-20129)