We study the elongation stage of mRNA translation in eukaryotes and find that, in contrast to the assumptions of previous models, both the supply and the demand for tRNA resources are important for determining elongation rates. We find that increasing the initiation rate of translation can lead to the depletion of some species of aa-tRNA, which in turn can lead to slow codons and queueing. Part...

Stm1p is a Saccharomyces cerevisiae protein that is primarily associated with cytosolic 80S ribosomes and polysomes. Several lines of evidence suggest that Stm1p plays a role in translation under nutrient stress conditions, although its mechanism of action is not yet known. In this study, we show that yeast lacking Stm1p (stm1Delta) are hypersensitive to the translation inhibitor anisomycin, wh...

Ribosomes are supramolecular ribonucleoprotein particles that synthesize proteins in all cells. Protein synthesis proceeds through four major phases: initiation, elongation, termination, and ribosome recycling. In each phase, a number of phase-specific translation factors cooperate with the ribosome. Whereas elongation in prokaryotes and eukaryotes involve similar factors and proceed by similar...

Synonymous codons encode the same amino acid, but differ in other biophysical properties. The evolutionary selection of codons whose properties are optimal for a cell generates the phenomenon of codon bias. Although recent studies have shown strong effects of codon usage changes on protein expression levels and cellular physiology, no translational control mechanism is known that links codon us...

Experimental studies of translation have found that short genes tend to exhibit greater densities of ribosomes than long genes in eukaryotic species. It remains an open question whether the elevated ribosome density on short genes is due to faster initiation or slower elongation dynamics. Here, we address this question computationally using 5'-mRNA folding energy as a proxy for translation init...

Messenger RNA (mRNA) secondary structure decreases the elongation rate, as ribosomes must unwind every structure they encounter during translation. Therefore, the strength of mRNA secondary structure is assumed to be reduced in highly translated mRNAs. However, previous studies in vitro reported a positive correlation between mRNA folding strength and protein abundance. The counterintuitive fin...

Translation is the fundamental biological process converting mRNA information into proteins. Single-molecule imaging in live cells has illuminated the dynamics of RNA transcription; however, it is not yet applicable to translation. Here, we report single-molecule imaging of nascent peptides (SINAPS) to assess translation in live cells. The approach provides direct readout of initiation, elongat...

Translation elongation plays a central role in multiple aspects of protein biogenesis, e.g., differential expression, cotranslational folding and secretion. However, our current understanding on the regulatory mechanisms underlying translation elongation dynamics and the functional roles of ribosome stalling in protein synthesis still remains largely limited. Here, we present a deep learning-ba...

Malaria parasites harbour two organelles with bacteria-like metabolic processes that are the targets of many anti-bacterial drugs. One such drug is fusidic acid, which inhibits the translation component elongation factor G. The response of P. falciparum to fusidic acid was characterised using extended SYBR-Green based drug trials. This revealed that fusidic acid kills in vitro cultured P. falci...