Limits...
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.

Show MeSH

Related in: MedlinePlus

Multivariate linear correlation among the relative abundances of mRNA, RNC-mRNA and protein. (A and B) Bivariate correlation comparing mRNA (A) and RNC-mRNA ratios (A549/HBE) (B) with SILAC ratio (A549/HBE), respectively. (C and D) Multivariate linear model, fitting SILAC ratio (A549/HBE), mRNA length and RNC-mRNA ratio (A549/HBE), calculated based on rpkM (C) and edgeR (D) normalizations regarding RNA-seq data. The viewpoints were on the fitted planes.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3643591&req=5

gkt178-F3: Multivariate linear correlation among the relative abundances of mRNA, RNC-mRNA and protein. (A and B) Bivariate correlation comparing mRNA (A) and RNC-mRNA ratios (A549/HBE) (B) with SILAC ratio (A549/HBE), respectively. (C and D) Multivariate linear model, fitting SILAC ratio (A549/HBE), mRNA length and RNC-mRNA ratio (A549/HBE), calculated based on rpkM (C) and edgeR (D) normalizations regarding RNA-seq data. The viewpoints were on the fitted planes.

Mentions: We observed that the mRNA ratio of A549 to HBE correlated poorly with the SILAC ratio (R2 = 0.37, Figure 3A), and that the correlation between the RNC-mRNA ratio and the SILAC ratio showed no increase (R2 = 0.31, Figure 3B). These results suggest that an extra factor must exist if our hypothesis on the tight correlation of mRNA/RNC-mRNA with protein abundance is true. We previously found that translation efficiency is affected by mRNA length (41), leading us to hypothesize that the mRNA length may serve as this additional factor. Therefore, we tested two multivariate linear models including mRNA length as candidates:(1)(2)where SR = SILAC ratio, MR = mRNA ratio, RR = RNC-mRNA ratio and L = mRNA length.Figure 3.


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)

Multivariate linear correlation among the relative abundances of mRNA, RNC-mRNA and protein. (A and B) Bivariate correlation comparing mRNA (A) and RNC-mRNA ratios (A549/HBE) (B) with SILAC ratio (A549/HBE), respectively. (C and D) Multivariate linear model, fitting SILAC ratio (A549/HBE), mRNA length and RNC-mRNA ratio (A549/HBE), calculated based on rpkM (C) and edgeR (D) normalizations regarding RNA-seq data. The viewpoints were on the fitted planes.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

gkt178-F3: Multivariate linear correlation among the relative abundances of mRNA, RNC-mRNA and protein. (A and B) Bivariate correlation comparing mRNA (A) and RNC-mRNA ratios (A549/HBE) (B) with SILAC ratio (A549/HBE), respectively. (C and D) Multivariate linear model, fitting SILAC ratio (A549/HBE), mRNA length and RNC-mRNA ratio (A549/HBE), calculated based on rpkM (C) and edgeR (D) normalizations regarding RNA-seq data. The viewpoints were on the fitted planes.
Mentions: We observed that the mRNA ratio of A549 to HBE correlated poorly with the SILAC ratio (R2 = 0.37, Figure 3A), and that the correlation between the RNC-mRNA ratio and the SILAC ratio showed no increase (R2 = 0.31, Figure 3B). These results suggest that an extra factor must exist if our hypothesis on the tight correlation of mRNA/RNC-mRNA with protein abundance is true. We previously found that translation efficiency is affected by mRNA length (41), leading us to hypothesize that the mRNA length may serve as this additional factor. Therefore, we tested two multivariate linear models including mRNA length as candidates:(1)(2)where SR = SILAC ratio, MR = mRNA ratio, RR = RNC-mRNA ratio and L = mRNA length.Figure 3.

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