In contrast to prokaryotes wherein GUG and UUG are permissive start codons, initiation frequencies from non-AUG codons are generally low in eukaryotes, with CUG being considered as strongest. Here, we report that combined 5-cytosine methylation (5mC) and pseudouridylation (Ψ) of near-cognate non-AUG start codons convert GUG and UUG initiation strongly favored over CUG initiation in eukaryotic translation under a certain context. This prokaryotic-like preference is attributed to enhanced NUG initiation by Ψ in the second base and reduced CUG initiation by 5mC in the first base.
View Article and Find Full Text PDFThe protein kinase Gcn2 is a central transducer of nutritional stress signaling important for stress adaptation by normal cells and the survival of cancer cells. In response to nutrient deprivation, Gcn2 phosphorylates eIF2α, thereby repressing general translation while enhancing translation of specific mRNAs with upstream ORFs (uORFs) situated in their 5'-leader regions. Here we performed genome-wide measurements of mRNA translation during histidine starvation in fission yeast Schizosaccharomyces pombe.
View Article and Find Full Text PDFObjective: To investigate a possible relationship between the oxytocin dose at caesarean section and blood loss.
Study Design: Retrospective analysis of computerised data for all caesarean sections in a UK maternity unit delivering 6000 women annually during 1995-2009 and thus for seven years before and after the 2001 recommended change in oxytocin dose. Validation of computerised and hand-checked clinical data for 1996 and 2006 was performed and annual frequency of blood loss >1000 ml was observed.