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Review
. 2012 Jun;13(4):294-304.
doi: 10.2174/138920312801619475.

RNA binding protein/RNA element interactions and the control of translation

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Free PMC article
Review

RNA binding protein/RNA element interactions and the control of translation

Xavier Pichon et al. Curr Protein Pept Sci. 2012 Jun.
Free PMC article

Abstract

A growing body of work demonstrates the importance of post-transcriptional control, in particular translation initiation, in the overall regulation of gene expression. Here we focus on the contribution of regulatory elements within the 5' and 3' untranslated regions of mRNA to gene expression in eukaryotic cells including terminal oligopyrimidine tracts, internal ribosome entry segments, upstream open reading frames and cytoplasmic polyadenylation elements. These mRNA regulatory elements may adopt complex secondary structures and/or contain sequence motifs that allow their interaction with a variety of regulatory proteins, RNAs and RNA binding proteins, particularly hnRNPs. The resulting interactions are context-sensitive, and provide cells with a sensitive and fast response to cellular signals such as hormone exposure or cytotoxic stress. Importantly, an increasing number of diseases have been identified, particularly cancers and those associated with neurodegeneration, which originate either from mutation of these regulatory motifs, or from deregulation of their cognate binding partners.

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Figures

Fig. (1)
Fig. (1)
Schematic representation of translation initiation regulation through cis elements and trans-acting factors acting in the mRNA 5’ UTR and 3’ UTR. Regulation through the 5’ UTR can occur via the 5’-Terminal Oligopyrimidine tracts (TOP) motif, Internal Ribosome Entry Sites (IRESs) and their IRES-trans-acting factors and upstream Open Reading Frames (uORFs). Regulation through the 3’ UTR can occur via the interaction of RNA-binding proteins (RBPs) with Protein-binding elements (PBEs), the interaction of the cytoplasmic polyadenylation element-binding-protein (CPEBP) with cytoplasmic polyadenylation element (CPE) and also via the interaction of poly(A)-binding protein (PABP) with the poly(A) tail, which leads to mRNA circularisation.

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