RNA Binding Protein/RNA Element Interactions and the Control of Translation

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.

SASH1, a new potential link between smoking and atherosclerosis

“…Despite its big size, only two polyadenylation signals were found, both in the 3'UTR region, at positions 4407 and 7685 respectively, suggesting that alternative splicing would only affect the length of the 3'UTR region. The 3'UTR region is known to contain a variety of regulatory regions that affects stability, localization, and translation efficiency of the transcript 102,103 . Consequently, while the two transcripts should result in the same protein sequence, their level of translation may differ.…”

Drift and conservation of differential exon usage across tissues in primate species

“…In particular, 5′ untranslated exons were subject to CTDU more than twice as often as expected from background 2. UTRs often contain regulatory elements, such as protein or miRNA binding sites, that are able to regulate translation and transcript localization (29). These results suggest that differential usage of UTRs has widespread effects, presumably in the posttranscriptional regulation of transcripts in a tissue-dependent manner.…”

Translation factors and ribosomal proteins control tumor onset and progression: how?

“…The general picture is still confusing because most of the interactions are remarkably cell-specific. 28 In spite of confusion, cell specificity is not artifactual from cellular models, but rather the key issue for targeting these factors. Indeed, it was found that a number of RNA-binding proteins that affect translation and/or mRNA stability are mutated in specific subtypes of cancer cells: prominent cases are Fam46c and Dis3 in multiple myeloma.…”