Attenuating ribosome load improves protein output from mRNA by limiting translation-dependent mRNA decay.

Developing an effective mRNA therapeutic often requires maximizing protein output per delivered mRNA molecule. We previously found that coding sequence (CDS) design can substantially affect protein output, with mRNA variants containing more optimal codons and higher secondary structure yielding the highest protein outputs due to their slow rates of mRNA decay. Here, we demonstrate that CDS-dependent differences in translation initiation and elongation rates lead to differences in translation- and deadenylation-dependent mRNA decay rates, thus explaining the effect of CDS on mRNA half-life.

Translation-dependent and -independent mRNA decay occur through mutually exclusive pathways defined by ribosome density during T cell activation.

mRNA translation and decay are tightly interconnected processes both in the context of mRNA quality-control pathways and for the degradation of functional mRNAs. Cotranslational mRNA degradation through codon usage, ribosome collisions, and the recruitment of specific proteins to ribosomes is an important determinant of mRNA turnover. However, the extent to which translation-dependent mRNA decay (TDD) and translation-independent mRNA decay (TID) pathways participate in the degradation of mRNAs has not been studied yet.

Market surveys and social media provide confirmation of the endangered giant freshwater whipray Urogymnus polylepis in Myanmar.

The giant freshwater whipray Urogymnus polylepis is a threatened species that is vulnerable to riverine and coastal marine pressures. Despite its threatened status, the range of U. polylepis is still being determined.

Rapid development of a salivary calculus in submandibular gland and its potential causes in a young victim following Russell's viper bite.

Russell's viper bites are known to cause a range of haemotoxic, neurotoxic, myotoxic, cytotoxic and nephrotoxic complications. However, the impact of Russell's viper bites as well as bites from other venomous snakes on sialolithiasis has not been previously reported. Here, we present an interesting case where a Russell's viper bite induced the rapid development of a calculus in submandibular gland in a 10-year-old boy.

Deep sequencing of pre-translational mRNPs reveals hidden flux through evolutionarily conserved alternative splicing nonsense-mediated decay pathways.

Background: Alternative splicing, which generates multiple mRNA isoforms from single genes, is crucial for the regulation of eukaryotic gene expression. The flux through competing splicing pathways cannot be determined by traditional RNA-Seq, however, because different mRNA isoforms can have widely differing decay rates. Indeed, some mRNA isoforms with extremely short half-lives, such as those subject to translation-dependent nonsense-mediated decay (AS-NMD), may be completely overlooked in even the most extensive RNA-Seq analyses.