title: Regulation of the expression and activity of Unr in mammalian cells.
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.
authors.affiliation: School of Life Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, U.K. e.c.anderson@warwick.ac.uk.
authors.forename: Emma C
authors.initials: EC
authors.lastname: Anderson
authors.affiliation: School of Life Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, U.K.
authors.forename: Pól Ó
authors.initials: PÓ
authors.lastname: Catnaigh
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000107:Acetylation; D017398:Alternative Splicing; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D010766:Phosphorylation; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; C079950:CSDE1 protein, human; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins
keywords: N-ras; alternative splicing; cold shock domain containing protein E1 (CSDE1); post-translational modification; translation; upstream of N-ras (Unr)