title: A perspective on mammalian upstream open reading frame function.
abstract: Post-transcriptional control makes a major contribution to the overall regulation of gene expression pathway. Within the cytoplasm this is mediated by a combination of regulatory RNA motifs within the 5' and 3' untranslated regions of mRNAs and their interacting protein/RNA partners. One of the most common regulatory RNA elements in mammalian transcripts (present in approximately 40% of all mRNAs) are upstream open reading frames (uORFs). However, despite the prevalence of these RNA elements how they function is not well understood. In general, they act to repress translation of the physiological ORF under control conditions, and under certain pathophysiological stresses this repression can be alleviated. It is known that re-initiation following the translation of an uORF is utilised in some situations however there are numerous alternative mechanisms that control the synthesis of a protein whose mRNA contains uORFs. Moreover, the trans-acting factors that are also involved in this process are not well defined. In this review we summarise our current understanding of this area and highlight some common features of these RNA motifs that have been discovered to date.
authors.affiliation: Medical Research Council Toxicology Unit, Leicester, United Kingdom. jks30@le.ac.uk
authors.forename: Joanna
authors.initials: J
authors.lastname: Somers
authors.forename: Tuija
authors.initials: T
authors.lastname: Pöyry
authors.forename: Anne E
authors.initials: AE
authors.lastname: Willis
mesh_terms: D000818:Animals; D003062:Codon / Q000235:genetics; D004194:Disease; D006801:Humans; D008322:Mammals / Q000235:genetics*; D008957:Models, Genetic; D016366:Open Reading Frames / Q000235:genetics*; D010442:Peptide Chain Initiation, Translational / Q000235:genetics
chemical_list: D003062:Codon
keywords: 4E-binding proteins; 4EBPs; AdoMetDCS; EMCV; Eif; IRES; NMD; Protein synthesis; RRL; SNP; THPO; Translational control; UTR; Upstream open reading frame; adenosyl-methionine decarboxylase; encephalomyocarditis virus; eukaryotic initiation factor; internal ribosome entry segment; nonsense mediated decay; rabbit reticulocyte lysate; single nucleotide polymorphism; thrombopoietin; uORF; untranslated region; upstream open reading frame