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Molecular genetic analysis of the RNA-mediated signaling pathways

RNA介导的信号通路的分子遗传学分析

基本信息

批准号：
17026034
负责人：
SUGIURA Reiko
金额：
$ 9.09万
依托单位：
Kinki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

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.

本研究旨在揭示RNA结合蛋白调控的信号转导途径的调控机制。我们利用裂解酵母模型系统和分子遗传学方法来鉴定调节包括MAP激酶通路在内的各种信号通路的RNA结合蛋白。我们鉴定了几种RNA结合蛋白，包括编码高度保守的KH型RNA结合蛋白的RnCL。RnCL过表达降低了Pmk1 MAPK信号的激活，RnCL缺失增加了Pmk1 MAPK信号的磷酸化水平，表明RnCL是Pmk1 MAPK信号的负调控因子。我们发现RnCL结合和稳定PMPL mRNA，PMPL mRNA编码Pmk1 MAPK的MAPK磷酸酶，并且Pmk1 MAPK使RnCL磷酸化，从而调节RnCL的RNA结合活性，从而结合和稳定PMPL mRNA。我们还鉴定了编码tRNA脱氨酶突变的tad3-1突变体。值得注意的是，我们发现Tad3-1突变体在细胞周期的G1/S和G2/M转变中表现出缺陷，从而表明摆动的tRNA修饰对分裂酵母的细胞周期是必不可少的。我们还鉴定了一种RRM型RNA结合蛋白，它稳定了编码肌动蛋白结合蛋白的mRNA。值得注意的是，MAPK Pmk1直接磷酸化RRM型RNA结合蛋白，这种磷酸化负向调节RNA结合蛋白与靶mRNAs结合的活性。长期以来，MAPK通路一直被认为是通过磷酸化各种转录因子来调节细胞信号的转录调节因子。我们的数据表明了一种新的范式，涉及MAPK介导的转录后RNA代谢的调节。

项目成果

期刊论文数量（61）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The role of the regulatory subunit of fission yeast calcineurin for in vivo activity and its relevance to FK506 sensitivity

DOI：
10.1074/jbc.m414234200
发表时间：
2005-04-01
期刊：
JOURNAL OF BIOLOGICAL CHEMISTRY
影响因子：
4.8
作者：
Sio, SO;Suehiro, T;Kuno, T
通讯作者：
Kuno, T

Real-time monitoring of calcineurin activity in living cells:: Evidence for two distinct Ca2+-dependent pathways in fission yeast

DOI：
10.1091/mbc.e06-06-0526
发表时间：
2006-11-01
期刊：
MOLECULAR BIOLOGY OF THE CELL
影响因子：
3.3
作者：
Deng, Lu;Sugiura, Reiko;Kuno, Takayoshi
通讯作者：
Kuno, Takayoshi

Atf1 Is a Target of the MAP Kinase Pmk1 and Regulates Cell Integrity in Fission Yeast.

Atf1 是 MAP 激酶 Pmk1 的靶标，可调节裂殖酵母中的细胞完整性。

DOI：
发表时间：
2007
期刊：
Mol. Biol. Cell 18
影响因子：
0
作者：
Y.Tonami;H.Murakami^* K.Shirahige;M.Nakanishi;Miyatake M et. al;Tsutsumi. et. al;Takada H et. al
通讯作者：
Takada H et. al

分裂酵母におけるPhosphoinositide dependent kinase (PDK)1ホモログの機能解析

裂殖酵母中磷酸肌醇依赖性激酶 (PDK)1 同源物的功能分析