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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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Biased TRs of BDP1 splice variants in A549 and HBE cells. (A and B) BDP1 splice variants detected in mRNA (A) and RNC-mRNA (B) of A549 and HBE cells, respectively. The bars represent the normalized number of reads that were mapped to specific splicing junctions of different variants. (C) TR of these splice variants in A549 and HBE cells, respectively.
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gkt178-F6: Biased TRs of BDP1 splice variants in A549 and HBE cells. (A and B) BDP1 splice variants detected in mRNA (A) and RNC-mRNA (B) of A549 and HBE cells, respectively. The bars represent the normalized number of reads that were mapped to specific splicing junctions of different variants. (C) TR of these splice variants in A549 and HBE cells, respectively.

Mentions: Proteomics and/or transcriptomics cannot address whether the genetic information of ASTs can be proportionally transmitted to translational level (44). However, comparison of the ASTs in mRNA and RNC-mRNA can reveal variant-specific TR information. We previously reported that ASTs of the BDP1 gene, coding one of the transcription factor IIIB subunits, exist with different abundances in various tissues (35). Therefore, we added RNC-mRNA information and analysed this gene again to serve as an example in this study (Figure 6). Consistent with our previous findings (35), we observed different and independent expression patterns of the BDP1 ASTs in both A549 and HBE cells at mRNA level (Figure 6A). These patterns were shifted at RNC-mRNA level in both cell lines (Figure 6B). Compared with other ASTs, the splice variant H5C7152.4 exhibited remarkably higher reads in the RNC-mRNA fraction than the mRNA fraction in A549 cells (Figure 6B). Furthermore, the splice variants H5C7152.5 and H5C7152.6 were less likely to be translated as their TRs ranged from 0.67 to 0.85, whereas the TR of H5C7152.4 reached 1.48 and 1.93 in A549 and HBE cells, respectively, evidencing a clear translational preference of this AST (Figure 6C). Collectively, the TR variance of the ASTs, either within a single cell type or across the two cell lines, displayed biased translation preference, suggesting a fine tuning in the genetic information transmission from mRNA to translation level.Figure 6.


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)

Biased TRs of BDP1 splice variants in A549 and HBE cells. (A and B) BDP1 splice variants detected in mRNA (A) and RNC-mRNA (B) of A549 and HBE cells, respectively. The bars represent the normalized number of reads that were mapped to specific splicing junctions of different variants. (C) TR of these splice variants in A549 and HBE cells, respectively.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
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gkt178-F6: Biased TRs of BDP1 splice variants in A549 and HBE cells. (A and B) BDP1 splice variants detected in mRNA (A) and RNC-mRNA (B) of A549 and HBE cells, respectively. The bars represent the normalized number of reads that were mapped to specific splicing junctions of different variants. (C) TR of these splice variants in A549 and HBE cells, respectively.
Mentions: Proteomics and/or transcriptomics cannot address whether the genetic information of ASTs can be proportionally transmitted to translational level (44). However, comparison of the ASTs in mRNA and RNC-mRNA can reveal variant-specific TR information. We previously reported that ASTs of the BDP1 gene, coding one of the transcription factor IIIB subunits, exist with different abundances in various tissues (35). Therefore, we added RNC-mRNA information and analysed this gene again to serve as an example in this study (Figure 6). Consistent with our previous findings (35), we observed different and independent expression patterns of the BDP1 ASTs in both A549 and HBE cells at mRNA level (Figure 6A). These patterns were shifted at RNC-mRNA level in both cell lines (Figure 6B). Compared with other ASTs, the splice variant H5C7152.4 exhibited remarkably higher reads in the RNC-mRNA fraction than the mRNA fraction in A549 cells (Figure 6B). Furthermore, the splice variants H5C7152.5 and H5C7152.6 were less likely to be translated as their TRs ranged from 0.67 to 0.85, whereas the TR of H5C7152.4 reached 1.48 and 1.93 in A549 and HBE cells, respectively, evidencing a clear translational preference of this AST (Figure 6C). Collectively, the TR variance of the ASTs, either within a single cell type or across the two cell lines, displayed biased translation preference, suggesting a fine tuning in the genetic information transmission from mRNA to translation level.Figure 6.

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