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Translating mRNAs strongly correlate to proteins in a multivariate manner and their translation ratios are phenotype specific.

Wang T, Cui Y, Jin J, Guo J, Wang G, Yin X, He QY, Zhang G - Nucleic Acids Res. (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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

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.

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Distribution and correlation analysis of mRNA TRs, comparing A549 cells with HBE cells. (A) Correlation of mRNA and RNC-mRNA abundances in A549 and HBE cells, respectively. (B) Correlation of mRNA ratio (A549/HBE) and RNC-mRNA ratio (A549/HBE). (C) Correlation of TRs and mRNA lengths. (D) Correlation of TR fold changes (A549/HBE) and mRNA lengths. The genes with TR ratio changes greater than 4 folds are indicated by green dots.
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gkt178-F4: Distribution and correlation analysis of mRNA TRs, comparing A549 cells with HBE cells. (A) Correlation of mRNA and RNC-mRNA abundances in A549 and HBE cells, respectively. (B) Correlation of mRNA ratio (A549/HBE) and RNC-mRNA ratio (A549/HBE). (C) Correlation of TRs and mRNA lengths. (D) Correlation of TR fold changes (A549/HBE) and mRNA lengths. The genes with TR ratio changes greater than 4 folds are indicated by green dots.

Mentions: This tight multivariate correlation between translating mRNAs and proteins suggests a close relationship between translational modulation and phenotypes. In this regard, gene-specific transfer of mRNA to ribosomes is an essential step in protein biogenesis. We then proceeded to analyse the TR changes of a total of 10 626 genes that were detected in A549 and HBE cells (Figure 4). Indeed, the mRNA abundances showed good correlation with RNC-mRNA abundances in both A549 and HBE cells (R2 were both greater than 0.85) (Figure 4A), whereas TR values did not correlate with mRNA abundances at all (R2 were approaching to 0) (Figure 4B).Figure 4.


Translating mRNAs strongly correlate to proteins in a multivariate manner and their translation ratios are phenotype specific.

Wang T, Cui Y, Jin J, Guo J, Wang G, Yin X, He QY, Zhang G - Nucleic Acids Res. (2013)

Distribution and correlation analysis of mRNA TRs, comparing A549 cells with HBE cells. (A) Correlation of mRNA and RNC-mRNA abundances in A549 and HBE cells, respectively. (B) Correlation of mRNA ratio (A549/HBE) and RNC-mRNA ratio (A549/HBE). (C) Correlation of TRs and mRNA lengths. (D) Correlation of TR fold changes (A549/HBE) and mRNA lengths. The genes with TR ratio changes greater than 4 folds are indicated by green dots.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3643591&req=5

gkt178-F4: Distribution and correlation analysis of mRNA TRs, comparing A549 cells with HBE cells. (A) Correlation of mRNA and RNC-mRNA abundances in A549 and HBE cells, respectively. (B) Correlation of mRNA ratio (A549/HBE) and RNC-mRNA ratio (A549/HBE). (C) Correlation of TRs and mRNA lengths. (D) Correlation of TR fold changes (A549/HBE) and mRNA lengths. The genes with TR ratio changes greater than 4 folds are indicated by green dots.
Mentions: This tight multivariate correlation between translating mRNAs and proteins suggests a close relationship between translational modulation and phenotypes. In this regard, gene-specific transfer of mRNA to ribosomes is an essential step in protein biogenesis. We then proceeded to analyse the TR changes of a total of 10 626 genes that were detected in A549 and HBE cells (Figure 4). Indeed, the mRNA abundances showed good correlation with RNC-mRNA abundances in both A549 and HBE cells (R2 were both greater than 0.85) (Figure 4A), whereas TR values did not correlate with mRNA abundances at all (R2 were approaching to 0) (Figure 4B).Figure 4.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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

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.

Show MeSH
Related in: MedlinePlus