Genome-wide Evaluation Of Translation Elongation Speed And Its Biological Significance

Proteins are the main carrier of life.Translation is the process of protein synthesis.In the process of translation,ribosomes first assemble on mRNAs(translation initiation)and then translate along the mRNA(elongation)to synthesize proteins.When ribosomes elongate to mRNA stop codon,translation will terminate.Some researches show that the regulation of elongation can influence the protein synthesis quality.Elongation pausing is deemed highly relevant to co-translational folding of nascent peptides and the functionality of protein products,which positioned the evaluation of elongation speed as one of the central questions in the field of translational control.The nonfunctional proteins may lead to human diseases.Unfortunately,there is no method to evaluate genome-wide translation elongation at individual gene level in physiological human cell.By integrating three types of RNA-seq methods,we experimentally and computationally resolved elongation speed,with our proposed elongation velocity index(EVI),a relative measure at individual gene level and under physiological condition in human cells.We successfully distinguished slow-translating genes from the background translatome.Interestingly,we didn't distinguish any genes which had both high TR and low EVI.We demonstrated that low-EVI genes encoded more stable proteins.We further identified cell-specific slow-translating codons,which might serve as a causal factor of elongation deceleration.As an example for the biological relevance,we showed that the relatively slow-translating genes tended to be associated with the maintenance of malignant phenotypes per pathway analyses.And the EVIs of TSGs were elevated significantly in more malignant cancer cell.In conclusion,EVI opens a new view to understand why human cells tend to avoid simultaneously speeding up translation initiation and decelerating elongation,and the possible cancer relevance of translating low-EVI genes to gain better protein quality.