Browsing by Issue Date, starting with "2015-07-27"
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- Resistance of mRNAs with AUG-proximal nonsense mutations to nonsense-mediated decay reflects variables of mRNA structure and translational activity.Publication . Pereira, Francisco; Kong, Jian; Siva, Ana Luísa; Liebhaber, Stephen A; Romão, LuísaNonsense-mediated mRNA decay (NMD) is a surveillance pathway that recognizes and selectively degrades mRNAs carrying premature termination codons (PTCs). The level of sensitivity of a PTC-containing mRNA to NMD is multifactorial. We have previously shown that human β-globin mRNAs carrying PTCs in close proximity to the translation initiation AUG codon escape NMD. This was called the 'AUG-proximity effect'. The present analysis of nonsense codons in the human α-globin mRNA illustrates that the determinants of the AUG-proximity effect are in fact quite complex, reflecting the ability of the ribosome to re-initiate translation 3' to the PTC and the specific sequence and secondary structure of the translated ORF. These data support a model in which the time taken to translate the short ORF, impacted by distance, sequence, and structure, not only modulates translation re-initiation, but also impacts on the exact boundary of AUG-proximity protection from NMD.
- Posttranscriptional Regulation and RNA Binding Proteins in Cancer BiologyPublication . Ghigna, Claudia; Cartegni, Luca; Jordan, Peter; Paronetto, Maria PaolaFollowing the completion of the human genome sequence and the concomitant technological innovations required for whole genome analyses, the last decade has witnessed an explosion of data and information concerning the posttranscriptional regulation of gene expression, in both pathological and nonpathological contexts. Among the most notable posttranscriptional events studied are the widespread usage of alternative splicing, the pleiotropic regulatory roles of miRNAs, and breakthroughs in the understanding of the control of gene expression by noncoding RNA transcripts. In this special issue of this journal, the spotlight is centered on the role that various mechanisms of posttranscriptional regulation—and the RNA binding proteins (RBPs) that control them—play in cancer biology.