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.
Highlights
Post-transcriptional control at the level of translation is an important mechanism by which gene expression can be regulated [1]
For many mRNAs initiation of translation occurs by a mechanism that has been termed cap-dependent scanning, which requires the binding of the trimeric complex eIF4F to the 7-methyl G cap structure, followed by ribosome scanning to the first AUG codon positioned within a good context [5, 6]
In erythroid precursor cells binding of heterogeneous nuclear ribonucleoprotein K and hnRNP E1 to the differentiation control element (DICE) in the 3’untranslated regions (UTRs) of r15-LOX mRNA leads to its translational repression by inhibiting the joining of the 60S subunit [76, 77]
Summary
Post-transcriptional control at the level of translation is an important mechanism by which gene expression can be regulated [1]. Alternative methods to initiate translation in mammalian cells have been described which require RNA motifs and specific interacting proteins that directly influence the translation of individual mRNAs. These include in the 5’ untranslated region (UTR) TOP-motifs, internal ribosome entry segments, upstream open reading frames and in the 3’ UTR a number of unique elements in addition to the poly a tail length (Fig. 1).
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