λN gene expression regulated by translation termination in ribosome L24 mutant

Besides transcription regulation, gene expression is also regulated at translation level. Although translation regulation is mainly mediated by translation initiation, an abundance of evi-dence shows that the termination phase of translation is also important for gene expression. The expression of lN gene is down regulated at translation level in L24 mutant, however the precise mechanism still remains unknown. We report here that in an L24 mutant strain, the expression of lac-lN and GST-lN is decreased to 25% and 50% of that in wild type T83 strain respectively. Strikingly, the yield of GST-lN fusion protein in L24 mutant can be restored to the level as in T83 wild type strain by changing the two codons upstream lN stop codon. These findings imply that the stop codon and its context are involved in the translation regulation. The possible reason is that the translation termination complex containing L24 mutant ribosome may not dissociate prop-erly in stop code region. This failure of disengagement from mRNA will slow down the process of following ribosomes, and consequently decrease the efficiency of lN gene expression.

Mechanistic insights into the alternative translation termination by ArfA and RF2

Subject Code:C05With the support by the National Natural Science Foundation of China,the research team led by Prof.Gao Ning(高宁)at the Ministry of Education Key Laboratory of Protein Sciences,Beijing Advanced Innovation Center for Structural Biology,School of Life Sciences,Tsinghua University,Beijing,recently reported how bacteria make use of a small protein called ArfA to rescue ribosomes stalled on defective messager RNAs,in Nature(2017,541:550—553).

Hemizygous deletion in the OTC gene results in ornithine transcarbamylase deficiency:A case report

BACKGROUND Ornithine transcarbamylase deficiency(OTCD)is a common ornithine cycle disorder,and OTC gene variation is the main pathogenic factor of this disease.This study explored and validated a variant in the OTC gene.CASE SUMMARY The neonate exhibited high blood ammonia,lactic acid,and homocysteine levels on the fifth day after birth.A novel deletion variant in the OTC gene[NM_000531.5,c.970_979delTTCCCAGAGG,p.Phe324GlnfsTer16]was uncovered by exome sequencing.The variant caused a protein-coding frameshift and resulted in early translation termination at the 16th amino acid after the variant site.CONCLUSION Our results provide a novel pathogenic variant in OTC and related clinical features for further OTCD screening and clinical consultation.

Distal nucleotides affect the rate of stop codon read-through

Background:A key step in gene expression is the recognition of the stop codon to terminate translation at the correct position.However,it has been observed that ribosomes can misinterpret the stop codon and continue the translation in the 3′UTR region.This phenomenon is called stop codon read-through(SCR).It has been suggested that these events would occur on a programmed basis,but the underlying mechanisms are still not well understood.Methods:Here,we present a strategy for the comprehensive identification of SCR events in the Drosophila melanogaster transcriptome by evaluating the ribosomal density profiles.The associated ribosomal leak rate was estimated for every event identified.A statistical characterization of the frequency of nucleotide use in the proximal region to the stop codon in the sequences associated to SCR events was performed.Results:The results show that the nucleotide usage pattern in transcripts with the UGA codon is different from the pattern for those transcripts ending in the UAA codon,suggesting the existence of at least two mechanisms that could alter the translational termination process.Furthermore,a linear regression models for each of the three stop codons was developed,and we show that the models using the nucleotides at informative positions outperforms those models that consider the entire sequence context to the stop codon.Conclusions:We report that distal nucleotides can affect the SCR rate in a stop-codon dependent manner.