title: 5'-UTR RNA G-quadruplexes: translation regulation and targeting.
abstract: RNA structures in the untranslated regions (UTRs) of mRNAs influence post-transcriptional regulation of gene expression. Much of the knowledge in this area depends on canonical double-stranded RNA elements. There has been considerable recent advancement of our understanding of guanine(G)-rich nucleic acids sequences that form four-stranded structures, called G-quadruplexes. While much of the research has been focused on DNA G-quadruplexes, there has recently been a rapid emergence of interest in RNA G-quadruplexes, particularly in the 5'-UTRs of mRNAs. Collectively, these studies suggest that RNA G-quadruplexes exist in the 5'-UTRs of many genes, including genes of clinical interest, and that such structural elements can influence translation. This review features the progresses in the study of 5'-UTR RNA G-quadruplex-mediated translational control. It covers computational analysis, cell-free, cell-based and chemical biology studies that have sought to elucidate the roles of RNA G-quadruplexes in both cap-dependent and -independent regulation of mRNA translation. We also discuss protein trans-acting factors that have been implicated and the evidence that such RNA motifs have potential as small molecule target. Finally, we close the review with a perspective on the future challenges in the field of 5'-UTR RNA G-quadruplex-mediated translation regulation.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. ab605@cam.ac.uk
authors.forename: Anthony
authors.initials: A
authors.lastname: Bugaut
authors.forename: Shankar
authors.initials: S
authors.lastname: Balasubramanian
mesh_terms: D020121:5' Untranslated Regions; D054856:G-Quadruplexes / Q000187:drug effects; D005786:Gene Expression Regulation; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D016601:RNA-Binding Proteins