Genome-Wide and Experimental Resolution of Relative Translation Elongation Speed at Individual Gene Level in Human Cells

PLoS Genet. 2016 Feb 29;12(2):e1005901. doi: 10.1371/journal.pgen.1005901. eCollection 2016 Feb.

Abstract

In the process of translation, ribosomes first assemble on mRNAs (translation initiation) and then translate along the mRNA (elongation) to synthesize proteins. 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. 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. 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. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Codon
  • Gene Expression
  • Genes, Tumor Suppressor
  • Genome, Human
  • HeLa Cells
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Peptide Chain Elongation, Translational / genetics*
  • Protein Stability
  • RNA, Messenger / genetics
  • Sequence Analysis, RNA

Substances

  • Codon
  • RNA, Messenger

Grants and funding

This work was supported by the National Basic Research Program “973” of China (2014CBA02000 to TW and 2011CB910700 to QYH), the National Natural and Science Foundation of China (81372135 to TW; 81322028 and 31300649 to GZ), the Institutional Grant of Excellence of Jinan University, China (50625072) to GZ as well as the Guangdong Natural Science Foundation (2014A030313369) and Guangzhou Key Subject (201504291059373) to TW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.