Regulation of the expression and activity of Unr in mammalian cells

Biochem Soc Trans. 2015 Dec;43(6):1241-6. doi: 10.1042/BST20150165.

Abstract

Unr (upstream of N-ras) is a post-transcriptional regulator of gene expression, essential for mammalian development and mutated in many human cancers. The expression of unr is itself regulated at many levels; transcription of unr, which also affects expression of the downstream N-ras gene, is tissue and developmental stage-dependent and is repressed by c-Myc and Max (Myc associated factor X). Alternative splicing gives rise to six transcript variants, which include three different 5'-UTRs. The transcripts are further diversified by the use of three alternative polyadenylation signals, which governs whether AU-rich instability elements are present in the 3'-UTR or not. Translation of at least some unr transcripts can occur by internal initiation and is regulated in a cell-cycle-dependent manner; binding of PTB (polypyrimidine tract-binding protein) and Unr to the 5'-UTR inhibits translation, but these are displaced by heterogeneous nuclear ribonucleoproteins C1/C2 (hnRNPC1/C2) during mitosis to stimulate translation. Finally, Unr is post-translationally modified by phosphorylation and lysine acetylation, although it is not yet known how these modifications affect Unr activity.

Keywords: N-ras; alternative splicing; cold shock domain containing protein E1 (CSDE1); post-translational modification; translation; upstream of N-ras (Unr).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Acetylation
  • Alternative Splicing
  • Animals
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Humans
  • Models, Genetic
  • Phosphorylation
  • Protein Biosynthesis*
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Transcription, Genetic*

Substances

  • 3' Untranslated Regions
  • CSDE1 protein, human
  • DNA-Binding Proteins
  • RNA-Binding Proteins