Protein kinase A regulates gene-specific translational adaptation in differentiating yeast
Cellular differentiation is driven by coordinately regulated changes in gene expression. Recent discoveries suggest that translation contributes as much as transcription to regulating protein abundance, but the role of translational regulation in cellular differentiation is largely unexplored. Here...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | en_US |
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Cold Spring Harbor Laboratory Press
2015
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| Online Access: | http://hdl.handle.net/1721.1/96901 https://orcid.org/0000-0003-2807-9657 https://orcid.org/0000-0002-4947-6048 |
| _version_ | 1811090875241988096 |
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| author | Vaidyanathan, Pavanapuresan P. Zinshteyn, Boris Thompson, Mary Katherine Gilbert, Wendy |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Vaidyanathan, Pavanapuresan P. Zinshteyn, Boris Thompson, Mary Katherine Gilbert, Wendy |
| author_sort | Vaidyanathan, Pavanapuresan P. |
| collection | MIT |
| description | Cellular differentiation is driven by coordinately regulated changes in gene expression. Recent discoveries suggest that translation contributes as much as transcription to regulating protein abundance, but the role of translational regulation in cellular differentiation is largely unexplored. Here we investigate translational reprogramming in yeast during cellular adaptation to the absence of glucose, a stimulus that induces invasive filamentous differentiation. Using ribosome footprint profiling and RNA sequencing to assay gene-specific translation activity genome-wide, we show that prolonged glucose withdrawal is accompanied by gene-specific changes in translational efficiency that significantly affect expression of the majority of genes. Notably, transcripts from a small minority (<5%) of genes make up the majority of translating mRNA in both rapidly dividing and starved differentiating cells, and the identities of these highly translated messages are almost nonoverlapping between conditions. Furthermore, these two groups of messages are subject to condition-dependent translational privilege. Thus the “housekeeping” process of translation does not stay constant during cellular differentiation but is highly adapted to different growth conditions. By comparing glucose starvation to growth-attenuating stresses that do not induce invasive filamentation, we distinguish a glucose-specific translational response mediated through signaling by protein kinase A (PKA). Together, these findings reveal a high degree of growth-state specialization of the translatome and identify PKA as an important regulator of gene-specific translation activity. |
| first_indexed | 2024-09-23T14:53:21Z |
| format | Article |
| id | mit-1721.1/96901 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:53:21Z |
| publishDate | 2015 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/969012022-09-29T11:13:56Z Protein kinase A regulates gene-specific translational adaptation in differentiating yeast Vaidyanathan, Pavanapuresan P. Zinshteyn, Boris Thompson, Mary Katherine Gilbert, Wendy Massachusetts Institute of Technology. Department of Biology Vaidyanathan, Pavanapuresan P. Zinshteyn, Boris Thompson, Mary Katherine Gilbert, Wendy Cellular differentiation is driven by coordinately regulated changes in gene expression. Recent discoveries suggest that translation contributes as much as transcription to regulating protein abundance, but the role of translational regulation in cellular differentiation is largely unexplored. Here we investigate translational reprogramming in yeast during cellular adaptation to the absence of glucose, a stimulus that induces invasive filamentous differentiation. Using ribosome footprint profiling and RNA sequencing to assay gene-specific translation activity genome-wide, we show that prolonged glucose withdrawal is accompanied by gene-specific changes in translational efficiency that significantly affect expression of the majority of genes. Notably, transcripts from a small minority (<5%) of genes make up the majority of translating mRNA in both rapidly dividing and starved differentiating cells, and the identities of these highly translated messages are almost nonoverlapping between conditions. Furthermore, these two groups of messages are subject to condition-dependent translational privilege. Thus the “housekeeping” process of translation does not stay constant during cellular differentiation but is highly adapted to different growth conditions. By comparing glucose starvation to growth-attenuating stresses that do not induce invasive filamentation, we distinguish a glucose-specific translational response mediated through signaling by protein kinase A (PKA). Together, these findings reveal a high degree of growth-state specialization of the translatome and identify PKA as an important regulator of gene-specific translation activity. National Institutes of Health (U.S.) (R01 GM094303) 2015-05-04T16:23:13Z 2015-05-04T16:23:13Z 2014-04 2014-01 Article http://purl.org/eprint/type/JournalArticle 1355-8382 1469-9001 http://hdl.handle.net/1721.1/96901 Vaidyanathan, P. P., B. Zinshteyn, M. K. Thompson, and W. V. Gilbert. “Protein Kinase A Regulates Gene-Specific Translational Adaptation in Differentiating Yeast.” RNA 20, no. 6 (April 23, 2014): 912–922. https://orcid.org/0000-0003-2807-9657 https://orcid.org/0000-0002-4947-6048 en_US http://dx.doi.org/10.1261/rna.044552.114 RNA Creative Commons Attribution http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Cold Spring Harbor Laboratory Press Cold Spring Harbor Laboratory Press |
| spellingShingle | Vaidyanathan, Pavanapuresan P. Zinshteyn, Boris Thompson, Mary Katherine Gilbert, Wendy Protein kinase A regulates gene-specific translational adaptation in differentiating yeast |
| title | Protein kinase A regulates gene-specific translational adaptation in differentiating yeast |
| title_full | Protein kinase A regulates gene-specific translational adaptation in differentiating yeast |
| title_fullStr | Protein kinase A regulates gene-specific translational adaptation in differentiating yeast |
| title_full_unstemmed | Protein kinase A regulates gene-specific translational adaptation in differentiating yeast |
| title_short | Protein kinase A regulates gene-specific translational adaptation in differentiating yeast |
| title_sort | protein kinase a regulates gene specific translational adaptation in differentiating yeast |
| url | http://hdl.handle.net/1721.1/96901 https://orcid.org/0000-0003-2807-9657 https://orcid.org/0000-0002-4947-6048 |
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