Sequence signatures and mRNA concentration can explain two‐thirds of protein abundance variation in a human cell line
Transcription, mRNA decay, translation and protein degradation are essential processes during eukaryotic gene expression, but their relative global contributions to steady‐state protein concentrations in multi‐cellular eukaryotes are largely unknown. Using measurements of absolute protein and mRNA a...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2010-01-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/msb.2010.59 |
| _version_ | 1797280754179244032 |
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| author | Christine Vogel Raquel de Sousa Abreu Daijin Ko Shu‐Yun Le Bruce A Shapiro Suzanne C Burns Devraj Sandhu Daniel R Boutz Edward M Marcotte Luiz O Penalva |
| author_facet | Christine Vogel Raquel de Sousa Abreu Daijin Ko Shu‐Yun Le Bruce A Shapiro Suzanne C Burns Devraj Sandhu Daniel R Boutz Edward M Marcotte Luiz O Penalva |
| author_sort | Christine Vogel |
| collection | DOAJ |
| description | Transcription, mRNA decay, translation and protein degradation are essential processes during eukaryotic gene expression, but their relative global contributions to steady‐state protein concentrations in multi‐cellular eukaryotes are largely unknown. Using measurements of absolute protein and mRNA abundances in cellular lysate from the human Daoy medulloblastoma cell line, we quantitatively evaluate the impact of mRNA concentration and sequence features implicated in translation and protein degradation on protein expression. Sequence features related to translation and protein degradation have an impact similar to that of mRNA abundance, and their combined contribution explains two‐thirds of protein abundance variation. mRNA sequence lengths, amino‐acid properties, upstream open reading frames and secondary structures in the 5′ untranslated region (UTR) were the strongest individual correlates of protein concentrations. In a combined model, characteristics of the coding region and the 3′UTR explained a larger proportion of protein abundance variation than characteristics of the 5′UTR. The absolute protein and mRNA concentration measurements for >1000 human genes described here represent one of the largest datasets currently available, and reveal both general trends and specific examples of post‐transcriptional regulation. |
| first_indexed | 2024-03-07T16:45:16Z |
| format | Article |
| id | doaj.art-dc169829b87448dca54dcc55130b453c |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T16:45:16Z |
| publishDate | 2010-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-dc169829b87448dca54dcc55130b453c2024-03-03T06:40:33ZengSpringer NatureMolecular Systems Biology1744-42922010-01-0161n/an/a10.1038/msb.2010.59Sequence signatures and mRNA concentration can explain two‐thirds of protein abundance variation in a human cell lineChristine Vogel0Raquel de Sousa Abreu1Daijin Ko2Shu‐Yun Le3Bruce A Shapiro4Suzanne C Burns5Devraj Sandhu6Daniel R Boutz7Edward M Marcotte8Luiz O Penalva9Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas Austin TX USAChildren's Cancer Research Institute, University of Texas Health Science Center San Antonio TX USADepartment of Management Science and Statistics, University of Texas San Antonio TX USACenter for Cancer Research Nanobiology Program, National Cancer Institute, NCI‐Frederick Frederick MD USACenter for Cancer Research Nanobiology Program, National Cancer Institute, NCI‐Frederick Frederick MD USAChildren's Cancer Research Institute, University of Texas Health Science Center San Antonio TX USAChildren's Cancer Research Institute, University of Texas Health Science Center San Antonio TX USACenter for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas Austin TX USACenter for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas Austin TX USAChildren's Cancer Research Institute, University of Texas Health Science Center San Antonio TX USATranscription, mRNA decay, translation and protein degradation are essential processes during eukaryotic gene expression, but their relative global contributions to steady‐state protein concentrations in multi‐cellular eukaryotes are largely unknown. Using measurements of absolute protein and mRNA abundances in cellular lysate from the human Daoy medulloblastoma cell line, we quantitatively evaluate the impact of mRNA concentration and sequence features implicated in translation and protein degradation on protein expression. Sequence features related to translation and protein degradation have an impact similar to that of mRNA abundance, and their combined contribution explains two‐thirds of protein abundance variation. mRNA sequence lengths, amino‐acid properties, upstream open reading frames and secondary structures in the 5′ untranslated region (UTR) were the strongest individual correlates of protein concentrations. In a combined model, characteristics of the coding region and the 3′UTR explained a larger proportion of protein abundance variation than characteristics of the 5′UTR. The absolute protein and mRNA concentration measurements for >1000 human genes described here represent one of the largest datasets currently available, and reveal both general trends and specific examples of post‐transcriptional regulation.https://doi.org/10.1038/msb.2010.59gene expression regulationprotein degradationprotein stabilitytranslation |
| spellingShingle | Christine Vogel Raquel de Sousa Abreu Daijin Ko Shu‐Yun Le Bruce A Shapiro Suzanne C Burns Devraj Sandhu Daniel R Boutz Edward M Marcotte Luiz O Penalva Sequence signatures and mRNA concentration can explain two‐thirds of protein abundance variation in a human cell line Molecular Systems Biology gene expression regulation protein degradation protein stability translation |
| title | Sequence signatures and mRNA concentration can explain two‐thirds of protein abundance variation in a human cell line |
| title_full | Sequence signatures and mRNA concentration can explain two‐thirds of protein abundance variation in a human cell line |
| title_fullStr | Sequence signatures and mRNA concentration can explain two‐thirds of protein abundance variation in a human cell line |
| title_full_unstemmed | Sequence signatures and mRNA concentration can explain two‐thirds of protein abundance variation in a human cell line |
| title_short | Sequence signatures and mRNA concentration can explain two‐thirds of protein abundance variation in a human cell line |
| title_sort | sequence signatures and mrna concentration can explain two thirds of protein abundance variation in a human cell line |
| topic | gene expression regulation protein degradation protein stability translation |
| url | https://doi.org/10.1038/msb.2010.59 |
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