title: Translating mRNAs strongly correlate to proteins in a multivariate manner and their translation ratios are phenotype specific.
abstract: As a well-known phenomenon, total mRNAs poorly correlate to proteins in their abundances as reported. Recent findings calculated with bivariate models suggested even poorer such correlation, whereas focusing on the translating mRNAs (ribosome nascent-chain complex-bound mRNAs, RNC-mRNAs) subset. In this study, we analysed the relative abundances of mRNAs, RNC-mRNAs and proteins on genome-wide scale, comparing human lung cancer A549 and H1299 cells with normal human bronchial epithelial (HBE) cells, respectively. As discovered, a strong correlation between RNC-mRNAs and proteins in their relative abundances could be established through a multivariate linear model by integrating the mRNA length as a key factor. The R(2) reached 0.94 and 0.97 in A549 versus HBE and H1299 versus HBE comparisons, respectively. This correlation highlighted that the mRNA length significantly contributes to the translational modulation, especially to the translational initiation, favoured by its correlation with the mRNA translation ratio (TR) as observed. We found TR is highly phenotype specific, which was substantiated by both pathway analysis and biased TRs of the splice variants of BDP1 gene, which is a key transcription factor of transfer RNAs. These findings revealed, for the first time, the intrinsic and genome-wide translation modulations at translatomic level in human cells at steady-state, which are tightly correlated to the protein abundance and functionally relevant to cellular phenotypes.
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China. tongwang@jnu.edu.cn
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Cui
authors.forename: Jingjie
authors.initials: J
authors.lastname: Jin
authors.forename: Jiahui
authors.initials: J
authors.lastname: Guo
authors.forename: Guibin
authors.initials: G
authors.lastname: Wang
authors.forename: Xingfeng
authors.initials: X
authors.lastname: Yin
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: He
authors.forename: Gong
authors.initials: G
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D016014:Linear Models; D015999:Multivariate Analysis; D010641:Phenotype; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis / Q000235:genetics; D020543:Proteome; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis* / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry; D017423:Sequence Analysis, RNA; D035361:Transcription Factor TFIIIB / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
chemical_list: C427472:BDP1 protein, human; D011506:Proteins; D020543:Proteome; D012333:RNA, Messenger; D035361:Transcription Factor TFIIIB