Article

5′-UTR RNA G-quadruplexes: translation regulation and targeting

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Nucleic Acids Research (Impact Factor: 9.11). 02/2012; 40(11):4727-41. DOI: 10.1093/nar/gks068
Source: PubMed

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.

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