Isoform‐resolved correlation analysis between mRNA abundance regulation and protein level degradation
Abstract Profiling of biological relationships between different molecular layers dissects regulatory mechanisms that ultimately determine cellular function. To thoroughly assess the role of protein post‐translational turnover, we devised a strategy combining pulse stable isotope‐labeled amino acids...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2020-03-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20199170 |
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| _version_ | 1849738329881313280 |
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| author | Barbora Salovska Hongwen Zhu Tejas Gandhi Max Frank Wenxue Li George Rosenberger Chongde Wu Pierre‐Luc Germain Hu Zhou Zdenek Hodny Lukas Reiter Yansheng Liu |
| author_facet | Barbora Salovska Hongwen Zhu Tejas Gandhi Max Frank Wenxue Li George Rosenberger Chongde Wu Pierre‐Luc Germain Hu Zhou Zdenek Hodny Lukas Reiter Yansheng Liu |
| author_sort | Barbora Salovska |
| collection | DOAJ |
| description | Abstract Profiling of biological relationships between different molecular layers dissects regulatory mechanisms that ultimately determine cellular function. To thoroughly assess the role of protein post‐translational turnover, we devised a strategy combining pulse stable isotope‐labeled amino acids in cells (pSILAC), data‐independent acquisition mass spectrometry (DIA‐MS), and a novel data analysis framework that resolves protein degradation rate on the level of mRNA alternative splicing isoforms and isoform groups. We demonstrated our approach by the genome‐wide correlation analysis between mRNA amounts and protein degradation across different strains of HeLa cells that harbor a high grade of gene dosage variation. The dataset revealed that specific biological processes, cellular organelles, spatial compartments of organelles, and individual protein isoforms of the same genes could have distinctive degradation rate. The protein degradation diversity thus dissects the corresponding buffering or concerting protein turnover control across cancer cell lines. The data further indicate that specific mRNA splicing events such as intron retention significantly impact the protein abundance levels. Our findings support the tight association between transcriptome variability and proteostasis and provide a methodological foundation for studying functional protein degradation. |
| format | Article |
| id | doaj-art-7eb9b1cb88724f28b0e02d5b8de1d4d0 |
| institution | DOAJ |
| issn | 1744-4292 |
| language | English |
| publishDate | 2020-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-7eb9b1cb88724f28b0e02d5b8de1d4d02025-08-20T03:06:39ZengSpringer NatureMolecular Systems Biology1744-42922020-03-0116311910.15252/msb.20199170Isoform‐resolved correlation analysis between mRNA abundance regulation and protein level degradationBarbora Salovska0Hongwen Zhu1Tejas Gandhi2Max Frank3Wenxue Li4George Rosenberger5Chongde Wu6Pierre‐Luc Germain7Hu Zhou8Zdenek Hodny9Lukas Reiter10Yansheng Liu11Yale Cancer Biology Institute, Yale UniversityDepartment of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesBiognosysEuropean Molecular Biology LaboratoryYale Cancer Biology Institute, Yale UniversityDepartment of Systems Biology, Columbia UniversityYale Cancer Biology Institute, Yale UniversityInstitute for Neuroscience, D‐HEST, ETH ZurichDepartment of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of SciencesDepartment of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of SciencesBiognosysYale Cancer Biology Institute, Yale UniversityAbstract Profiling of biological relationships between different molecular layers dissects regulatory mechanisms that ultimately determine cellular function. To thoroughly assess the role of protein post‐translational turnover, we devised a strategy combining pulse stable isotope‐labeled amino acids in cells (pSILAC), data‐independent acquisition mass spectrometry (DIA‐MS), and a novel data analysis framework that resolves protein degradation rate on the level of mRNA alternative splicing isoforms and isoform groups. We demonstrated our approach by the genome‐wide correlation analysis between mRNA amounts and protein degradation across different strains of HeLa cells that harbor a high grade of gene dosage variation. The dataset revealed that specific biological processes, cellular organelles, spatial compartments of organelles, and individual protein isoforms of the same genes could have distinctive degradation rate. The protein degradation diversity thus dissects the corresponding buffering or concerting protein turnover control across cancer cell lines. The data further indicate that specific mRNA splicing events such as intron retention significantly impact the protein abundance levels. Our findings support the tight association between transcriptome variability and proteostasis and provide a methodological foundation for studying functional protein degradation.https://doi.org/10.15252/msb.20199170alternative splicingDIA mass spectrometryprotein turnoverproteomicspulsed SILAC |
| spellingShingle | Barbora Salovska Hongwen Zhu Tejas Gandhi Max Frank Wenxue Li George Rosenberger Chongde Wu Pierre‐Luc Germain Hu Zhou Zdenek Hodny Lukas Reiter Yansheng Liu Isoform‐resolved correlation analysis between mRNA abundance regulation and protein level degradation Molecular Systems Biology alternative splicing DIA mass spectrometry protein turnover proteomics pulsed SILAC |
| title | Isoform‐resolved correlation analysis between mRNA abundance regulation and protein level degradation |
| title_full | Isoform‐resolved correlation analysis between mRNA abundance regulation and protein level degradation |
| title_fullStr | Isoform‐resolved correlation analysis between mRNA abundance regulation and protein level degradation |
| title_full_unstemmed | Isoform‐resolved correlation analysis between mRNA abundance regulation and protein level degradation |
| title_short | Isoform‐resolved correlation analysis between mRNA abundance regulation and protein level degradation |
| title_sort | isoform resolved correlation analysis between mrna abundance regulation and protein level degradation |
| topic | alternative splicing DIA mass spectrometry protein turnover proteomics pulsed SILAC |
| url | https://doi.org/10.15252/msb.20199170 |
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