2006 Fiscal Year Final Research Report Summary
Molecular genetic analysis of the RNA-mediated signaling pathways
| Project/Area Number |
17026034
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kinki University |
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Principal Investigator |
SUGIURA Reiko Kinki University, 薬学部, Professor (90294206)
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| Project Period (FY) |
2005 – 2006
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| Keywords | RNA-binding protein / MAP kinase signalling / fission yeast / protein phosp hory lation / mRNA stability |
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| Research Abstract |
This research aims to unravel the regulatory mechanisms of the signal transduction pathway regulated by RNA-binding proteins. We utilized the fission yeast model system and molecular genetic approach to identify RNA binding proteins that regulate various signaling pathways including MAP kinase pathways. We identified several RNA-binding proteins including Rncl that encodes a highly conserved KH-type RNA-binding protein. Rncl overexpression decreased the activation of the Pmkl MAPK signaling and Rncl deletion increased the phosphorylation level of the Pmk1 MAPK signaling thus indicating that Rncl acts as a negative regulator of the Pmkl MAPK signaling. We demonstrated that Rncl binds and stabilizes Pmpl mRNA that encodes a MAPK phosphatase for Pmkl MAPK Moreover, Pmk1 MAPK phosphorylates Rncl which regulates the RNA-binding activity of Rncl to bind and stabilize Pmpl mRNA. We also identified the tad3-1 mutant that encodes a mutation in the tRNA deaminase. Notably, we demonstrated that the tad3-1 mutants displayed defects in cell cycle progression at G1/S and G2/M transitions thus indicating that the wobble tRNA modification is essential to cell cycle in fission yeast. We also identified an RRM-type RNA binding protein that stabilizes the mRNA encoding an actin-binding protein. Notably, the MAPK Pmk1 directly phosphorylates the RRM-type RNA-binding protein and this phosphorylation negatively regulates the activity of the RNA-binding protein to bind target mRNAs. The MAPK pathways have long been known as a transcriptional regulator of cellular signaling by phosphorylating various transcription factors. Our data suggest a novel paradigm involving the MAPK-mediated regulation of the post-transcriptional RNAmetabolism.
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Research Products
(52 results)
