Most organisms use different mechanisms of translation termination for the three types of stop codons, i.e. UAA, UAG, and UGA [1]. Using the GenBank database, we have conducted comprehensive computer analyses of translation termination sites in order to find the difference of consensus sequence patterns around each type of stop codons. We also systematically analyzed the preference of stop codo...

In contrast to bacteria that have two release factors, RF1 and RF2, eukaryotes only possess one unrelated release factor eRF1, which recognizes all three stop codons of the mRNA and hydrolyses the peptidyl-tRNA bond. While the molecular basis for bacterial termination has been elucidated, high-resolution structures of eukaryotic termination complexes have been lacking. Here we present a 3.8 Å s...

A limited number of non-canonical genetic codes have been described in eukaryotic nuclear genomes. Most involve reassignment of one or two termination codons as sense ones [1-4], but no code variant is known that would have reassigned all three termination codons. Here, we describe such a variant that we discovered in a clade of trypanosomatids comprising nominal Blastocrithidia species. In the...

Protein output from synonymous codons is thought to be equivalent if appropriate tRNAs are sufficiently abundant. Here we show that mRNAs encoding iterated lysine codons, AAA or AAG, differentially impact protein synthesis: insertion of iterated AAA codons into an ORF diminishes protein expression more than insertion of synonymous AAG codons. Kinetic studies in E. coli reveal that differential ...

Human mitochondria are not strict adherents to the universal genetic code, with modifications that include the apparent recoding of two arginine triplets to termination signals. This use of both AGA and AGG occurs rarely in other mammals, and this putative change has long posed a challenging conundrum. A -1 mitoribosome frameshift upstream of the rare codons would necessitate recognition of onl...

The considerable range of genetic variation in human populations may partly reflect distinctive processes of adaptation to variable environmental conditions. However, the adaptive genomic signatures remain to be completely elucidated. This research explores candidate loci under selection at the population level by characterizing recently arisen premature termination codons (PTCs), some of which...

Translation termination at premature termination codons (PTCs) triggers degradation of the aberrant mRNA, but the mechanism by which a termination event is defined as premature is still unclear. Here we show that the physical distance between the termination codon and the poly(A)-binding protein PABPC1 is a crucial determinant for PTC recognition in human cells. "Normal" termination codons can ...