title: Genome-Wide and Experimental Resolution of Relative Translation Elongation Speed at Individual Gene Level in Human Cells.
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.
authors.affiliation: Institute of Life and Health Engineering, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou, China.
authors.forename: Xinlei
authors.initials: X
authors.lastname: Lian
authors.affiliation: Institute of Life and Health Engineering, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Guo
authors.affiliation: Institute of Life and Health Engineering, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.affiliation: Institute of Life and Health Engineering, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Institute of Life and Health Engineering, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou, China.
authors.forename: Jiayong
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Institute of Life and Health Engineering, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou, China.
authors.forename: Jingjie
authors.initials: J
authors.lastname: Jin
authors.affiliation: Institute of Life and Health Engineering, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou, China.
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: He
authors.affiliation: Institute of Life and Health Engineering, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institute of Life and Health Engineering, Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D003062:Codon; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D010441:Peptide Chain Elongation, Translational / Q000235:genetics*; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics; D017423:Sequence Analysis, RNA
chemical_list: D003062:Codon; D012333:RNA, Messenger