Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress
Abstract The relative importance of regulation at the mRNA versus protein level is subject to ongoing debate. To address this question in a dynamic system, we mapped proteomic and transcriptomic changes in mammalian cells responding to stress induced by dithiothreitol over 30 h. Specifically, we est...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2016-01-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.20156423 |
| _version_ | 1797280519659978752 |
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| author | Zhe Cheng Guoshou Teo Sabrina Krueger Tara M Rock Hiromi WL Koh Hyungwon Choi Christine Vogel |
| author_facet | Zhe Cheng Guoshou Teo Sabrina Krueger Tara M Rock Hiromi WL Koh Hyungwon Choi Christine Vogel |
| author_sort | Zhe Cheng |
| collection | DOAJ |
| description | Abstract The relative importance of regulation at the mRNA versus protein level is subject to ongoing debate. To address this question in a dynamic system, we mapped proteomic and transcriptomic changes in mammalian cells responding to stress induced by dithiothreitol over 30 h. Specifically, we estimated the kinetic parameters for the synthesis and degradation of RNA and proteins, and deconvoluted the response patterns into common and unique to each regulatory level using a new statistical tool. Overall, the two regulatory levels were equally important, but differed in their impact on molecule concentrations. Both mRNA and protein changes peaked between two and eight hours, but mRNA expression fold changes were much smaller than those of the proteins. mRNA concentrations shifted in a transient, pulse‐like pattern and returned to values close to pre‐treatment levels by the end of the experiment. In contrast, protein concentrations switched only once and established a new steady state, consistent with the dominant role of protein regulation during misfolding stress. Finally, we generated hypotheses on specific regulatory modes for some genes. |
| first_indexed | 2024-03-07T16:41:26Z |
| format | Article |
| id | doaj.art-87ee4bce42c64c1aadca88a1903ac0f4 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T16:41:26Z |
| publishDate | 2016-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-87ee4bce42c64c1aadca88a1903ac0f42024-03-03T08:12:02ZengSpringer NatureMolecular Systems Biology1744-42922016-01-01121n/an/a10.15252/msb.20156423Differential dynamics of the mammalian mRNA and protein expression response to misfolding stressZhe Cheng0Guoshou Teo1Sabrina Krueger2Tara M Rock3Hiromi WL Koh4Hyungwon Choi5Christine Vogel6Center for Genomics and Systems Biology New York University New York NY USASaw Swee Hock School of Public Health National University Singapore SingaporeBerlin Institute for Medical Systems Biology Max Delbrück Center for Molecular Medicine Berlin GermanyCenter for Genomics and Systems Biology New York University New York NY USASaw Swee Hock School of Public Health National University Singapore SingaporeSaw Swee Hock School of Public Health National University Singapore SingaporeCenter for Genomics and Systems Biology New York University New York NY USAAbstract The relative importance of regulation at the mRNA versus protein level is subject to ongoing debate. To address this question in a dynamic system, we mapped proteomic and transcriptomic changes in mammalian cells responding to stress induced by dithiothreitol over 30 h. Specifically, we estimated the kinetic parameters for the synthesis and degradation of RNA and proteins, and deconvoluted the response patterns into common and unique to each regulatory level using a new statistical tool. Overall, the two regulatory levels were equally important, but differed in their impact on molecule concentrations. Both mRNA and protein changes peaked between two and eight hours, but mRNA expression fold changes were much smaller than those of the proteins. mRNA concentrations shifted in a transient, pulse‐like pattern and returned to values close to pre‐treatment levels by the end of the experiment. In contrast, protein concentrations switched only once and established a new steady state, consistent with the dominant role of protein regulation during misfolding stress. Finally, we generated hypotheses on specific regulatory modes for some genes.https://doi.org/10.15252/msb.20156423Central DogmaER stressmammalian proteomicsmass spectrometryPECA |
| spellingShingle | Zhe Cheng Guoshou Teo Sabrina Krueger Tara M Rock Hiromi WL Koh Hyungwon Choi Christine Vogel Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress Molecular Systems Biology Central Dogma ER stress mammalian proteomics mass spectrometry PECA |
| title | Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress |
| title_full | Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress |
| title_fullStr | Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress |
| title_full_unstemmed | Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress |
| title_short | Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress |
| title_sort | differential dynamics of the mammalian mrna and protein expression response to misfolding stress |
| topic | Central Dogma ER stress mammalian proteomics mass spectrometry PECA |
| url | https://doi.org/10.15252/msb.20156423 |
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