RNA-Binding Protein Rnc1 Regulates Cell Length at Division and Acute Stress Response in Fission Yeast through Negative Feedback Modulation of the Stress-Activated Mitogen-Activated Protein Kinase Pathway
ABSTRACT RNA-binding proteins (RBPs) play a major role during control of mRNA localization, stability, and translation and are central to most cellular processes. In the fission yeast Schizosaccharomyces pombe, the multiple K homology (KH) domain RBP Rnc1 downregulates the activity of the cell integ...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-02-01
|
| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02815-19 |
| _version_ | 1818419731798949888 |
|---|---|
| author | Francisco Prieto-Ruiz Jero Vicente-Soler Alejandro Franco Elisa Gómez-Gil Marta Sánchez-Marinas Beatriz Vázquez-Marín Rosa Aligué Marisa Madrid Sergio Moreno Teresa Soto José Cansado |
| author_facet | Francisco Prieto-Ruiz Jero Vicente-Soler Alejandro Franco Elisa Gómez-Gil Marta Sánchez-Marinas Beatriz Vázquez-Marín Rosa Aligué Marisa Madrid Sergio Moreno Teresa Soto José Cansado |
| author_sort | Francisco Prieto-Ruiz |
| collection | DOAJ |
| description | ABSTRACT RNA-binding proteins (RBPs) play a major role during control of mRNA localization, stability, and translation and are central to most cellular processes. In the fission yeast Schizosaccharomyces pombe, the multiple K homology (KH) domain RBP Rnc1 downregulates the activity of the cell integrity pathway (CIP) via stabilization of pmp1+ mRNA, which encodes the Pmp1 phosphatase that inactivates Pmk1, the mitogen-activated protein kinase (MAPK) component of this signaling cascade. However, Rnc1 likely regulates the half-life/stability of additional mRNAs. We show that Rnc1 downregulates the activity of Sty1, the MAPK of the stress-activated MAPK pathway (SAPK), during control of cell length at division and recovery in response to acute stress. Importantly, this control strictly depends on Rnc1’s ability to bind mRNAs encoding activators (Wak1 MAPKKK, Wis1 MAPKK) and downregulators (Atf1 transcription factor, Pyp1 and Pyp2 phosphatases) of Sty1 phosphorylation through its KH domains. Moreover, Sty1 is responsible for Rnc1 phosphorylation in vivo at multiple phosphosites during growth and stress, and these modifications trigger Rnc1 for proper binding and destabilization of the above mRNA targets. Phosphorylation by Sty1 prompts Rnc1-dependent mRNA destabilization to negatively control SAPK signaling, thus revealing an additional feedback mechanism that allows precise tuning of MAPK activity during unperturbed cell growth and stress. IMPORTANCE Control of mRNA localization, stability, turnover, and translation by RNA-binding proteins (RBPs) influences essential processes in all eukaryotes, including signaling by mitogen-activated protein kinase (MAPK) pathways. We describe that in the fission yeast Schizosaccharomyces pombe the RBP Rnc1 negatively regulates cell length at division during unperturbed growth and recovery after acute stress by reducing the activity of the MAPK Sty1, which regulates cell growth and differentiation during environmental cues. This mechanism relies on Rnc1 binding to specific mRNAs encoding both enhancers and negative regulators of Sty1 activity. Remarkably, multiple phosphorylation of Rnc1 by Sty1 favors RBP binding and destabilization of the above mRNAs. Thus, posttranscriptional modulation of MAP kinase signaling by RNA-binding proteins emerges as a major regulatory mechanism that dictates the growth cycle and cellular adaptation in response to the changing environment in eukaryotic organisms. |
| first_indexed | 2024-12-14T12:43:14Z |
| format | Article |
| id | doaj.art-9d13c7c0bb394d0ab8d78fc2da79ef3a |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T12:43:14Z |
| publishDate | 2020-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-9d13c7c0bb394d0ab8d78fc2da79ef3a2022-12-21T23:00:50ZengAmerican Society for MicrobiologymBio2150-75112020-02-0111110.1128/mBio.02815-19RNA-Binding Protein Rnc1 Regulates Cell Length at Division and Acute Stress Response in Fission Yeast through Negative Feedback Modulation of the Stress-Activated Mitogen-Activated Protein Kinase PathwayFrancisco Prieto-Ruiz0Jero Vicente-Soler1Alejandro Franco2Elisa Gómez-Gil3Marta Sánchez-Marinas4Beatriz Vázquez-Marín5Rosa Aligué6Marisa Madrid7Sergio Moreno8Teresa Soto9José Cansado10Yeast Physiology Group, Departmento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, Murcia, SpainYeast Physiology Group, Departmento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, Murcia, SpainYeast Physiology Group, Departmento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, Murcia, SpainYeast Physiology Group, Departmento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, Murcia, SpainDepartment of Biomedical Sciences, Facultat de Medicina, Universidad de Barcelona, Barcelona, SpainYeast Physiology Group, Departmento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, Murcia, SpainDepartment of Biomedical Sciences, Facultat de Medicina, Universidad de Barcelona, Barcelona, SpainYeast Physiology Group, Departmento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, Murcia, SpainInstituto de Biología Funcional y Genómica (IBFG), Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Salamanca, SpainYeast Physiology Group, Departmento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, Murcia, SpainYeast Physiology Group, Departmento de Genética y Microbiología, Facultad de Biología, Universidad de Murcia, Murcia, SpainABSTRACT RNA-binding proteins (RBPs) play a major role during control of mRNA localization, stability, and translation and are central to most cellular processes. In the fission yeast Schizosaccharomyces pombe, the multiple K homology (KH) domain RBP Rnc1 downregulates the activity of the cell integrity pathway (CIP) via stabilization of pmp1+ mRNA, which encodes the Pmp1 phosphatase that inactivates Pmk1, the mitogen-activated protein kinase (MAPK) component of this signaling cascade. However, Rnc1 likely regulates the half-life/stability of additional mRNAs. We show that Rnc1 downregulates the activity of Sty1, the MAPK of the stress-activated MAPK pathway (SAPK), during control of cell length at division and recovery in response to acute stress. Importantly, this control strictly depends on Rnc1’s ability to bind mRNAs encoding activators (Wak1 MAPKKK, Wis1 MAPKK) and downregulators (Atf1 transcription factor, Pyp1 and Pyp2 phosphatases) of Sty1 phosphorylation through its KH domains. Moreover, Sty1 is responsible for Rnc1 phosphorylation in vivo at multiple phosphosites during growth and stress, and these modifications trigger Rnc1 for proper binding and destabilization of the above mRNA targets. Phosphorylation by Sty1 prompts Rnc1-dependent mRNA destabilization to negatively control SAPK signaling, thus revealing an additional feedback mechanism that allows precise tuning of MAPK activity during unperturbed cell growth and stress. IMPORTANCE Control of mRNA localization, stability, turnover, and translation by RNA-binding proteins (RBPs) influences essential processes in all eukaryotes, including signaling by mitogen-activated protein kinase (MAPK) pathways. We describe that in the fission yeast Schizosaccharomyces pombe the RBP Rnc1 negatively regulates cell length at division during unperturbed growth and recovery after acute stress by reducing the activity of the MAPK Sty1, which regulates cell growth and differentiation during environmental cues. This mechanism relies on Rnc1 binding to specific mRNAs encoding both enhancers and negative regulators of Sty1 activity. Remarkably, multiple phosphorylation of Rnc1 by Sty1 favors RBP binding and destabilization of the above mRNAs. Thus, posttranscriptional modulation of MAP kinase signaling by RNA-binding proteins emerges as a major regulatory mechanism that dictates the growth cycle and cellular adaptation in response to the changing environment in eukaryotic organisms.https://journals.asm.org/doi/10.1128/mBio.02815-19MAP kinasesRNA-binding proteinsfission yeast |
| spellingShingle | Francisco Prieto-Ruiz Jero Vicente-Soler Alejandro Franco Elisa Gómez-Gil Marta Sánchez-Marinas Beatriz Vázquez-Marín Rosa Aligué Marisa Madrid Sergio Moreno Teresa Soto José Cansado RNA-Binding Protein Rnc1 Regulates Cell Length at Division and Acute Stress Response in Fission Yeast through Negative Feedback Modulation of the Stress-Activated Mitogen-Activated Protein Kinase Pathway mBio MAP kinases RNA-binding proteins fission yeast |
| title | RNA-Binding Protein Rnc1 Regulates Cell Length at Division and Acute Stress Response in Fission Yeast through Negative Feedback Modulation of the Stress-Activated Mitogen-Activated Protein Kinase Pathway |
| title_full | RNA-Binding Protein Rnc1 Regulates Cell Length at Division and Acute Stress Response in Fission Yeast through Negative Feedback Modulation of the Stress-Activated Mitogen-Activated Protein Kinase Pathway |
| title_fullStr | RNA-Binding Protein Rnc1 Regulates Cell Length at Division and Acute Stress Response in Fission Yeast through Negative Feedback Modulation of the Stress-Activated Mitogen-Activated Protein Kinase Pathway |
| title_full_unstemmed | RNA-Binding Protein Rnc1 Regulates Cell Length at Division and Acute Stress Response in Fission Yeast through Negative Feedback Modulation of the Stress-Activated Mitogen-Activated Protein Kinase Pathway |
| title_short | RNA-Binding Protein Rnc1 Regulates Cell Length at Division and Acute Stress Response in Fission Yeast through Negative Feedback Modulation of the Stress-Activated Mitogen-Activated Protein Kinase Pathway |
| title_sort | rna binding protein rnc1 regulates cell length at division and acute stress response in fission yeast through negative feedback modulation of the stress activated mitogen activated protein kinase pathway |
| topic | MAP kinases RNA-binding proteins fission yeast |
| url | https://journals.asm.org/doi/10.1128/mBio.02815-19 |
| work_keys_str_mv | AT franciscoprietoruiz rnabindingproteinrnc1regulatescelllengthatdivisionandacutestressresponseinfissionyeastthroughnegativefeedbackmodulationofthestressactivatedmitogenactivatedproteinkinasepathway AT jerovicentesoler rnabindingproteinrnc1regulatescelllengthatdivisionandacutestressresponseinfissionyeastthroughnegativefeedbackmodulationofthestressactivatedmitogenactivatedproteinkinasepathway AT alejandrofranco rnabindingproteinrnc1regulatescelllengthatdivisionandacutestressresponseinfissionyeastthroughnegativefeedbackmodulationofthestressactivatedmitogenactivatedproteinkinasepathway AT elisagomezgil rnabindingproteinrnc1regulatescelllengthatdivisionandacutestressresponseinfissionyeastthroughnegativefeedbackmodulationofthestressactivatedmitogenactivatedproteinkinasepathway AT martasanchezmarinas rnabindingproteinrnc1regulatescelllengthatdivisionandacutestressresponseinfissionyeastthroughnegativefeedbackmodulationofthestressactivatedmitogenactivatedproteinkinasepathway AT beatrizvazquezmarin rnabindingproteinrnc1regulatescelllengthatdivisionandacutestressresponseinfissionyeastthroughnegativefeedbackmodulationofthestressactivatedmitogenactivatedproteinkinasepathway AT rosaaligue rnabindingproteinrnc1regulatescelllengthatdivisionandacutestressresponseinfissionyeastthroughnegativefeedbackmodulationofthestressactivatedmitogenactivatedproteinkinasepathway AT marisamadrid rnabindingproteinrnc1regulatescelllengthatdivisionandacutestressresponseinfissionyeastthroughnegativefeedbackmodulationofthestressactivatedmitogenactivatedproteinkinasepathway AT sergiomoreno rnabindingproteinrnc1regulatescelllengthatdivisionandacutestressresponseinfissionyeastthroughnegativefeedbackmodulationofthestressactivatedmitogenactivatedproteinkinasepathway AT teresasoto rnabindingproteinrnc1regulatescelllengthatdivisionandacutestressresponseinfissionyeastthroughnegativefeedbackmodulationofthestressactivatedmitogenactivatedproteinkinasepathway AT josecansado rnabindingproteinrnc1regulatescelllengthatdivisionandacutestressresponseinfissionyeastthroughnegativefeedbackmodulationofthestressactivatedmitogenactivatedproteinkinasepathway |