一种对营养物质反应的途径,通过控制B-环素mRNA稳定性来确定M阶段时间
Vincent Messier1, Daniel Zenklusen, Stephen W Michnick
1Département de Biochimie, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec H3C 3J7, Canada.
Cell
|May 28, 2013
概括
酵母细胞周期的进展依赖于调节CLB2mRNA水平. 蛋白Hmt1稳定CLB2mRNA,其活性由Dbf2激酶和Pph22酸酶控制,影响营养物质变化期间的细胞分裂.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 细胞循环的进展需要精确调节基因表达以响应环境线索,如营养的可用性.
- M相环林CLB2是酵母细胞分裂的关键调节剂.
- 翻译后的修改,如氨酸甲基化,在调节蛋白质功能和mRNA稳定性方面发挥作用.
研究的目的:
- 研究CLB2mRNA积累受营养水平调节的机制.
- 确定参与控制CLB2mRNA稳定性的关键蛋白质及其调节相互作用.
- 阐明氨酸甲基转移酶Hmt1在M相环林调节中的作用.
主要方法:
- 使用了酵母遗传学和分子生物学技术.
- 使用北方涂抹和定量PCR分析CLB2mRNA水平.
- 研究蛋白质-蛋白质相互作用和酶活动 (酶,酸酶,甲基转移酶).
- 研究营养缺乏和TOR抑制对细胞循环进展的影响.
主要成果:
- CLB2 mRNA积累取决于Hmt1的组装和激活,Hmt1是一种异质的核RNA结合蛋白 (hnRNP) 氨酸甲基转移酶.
- Hmt1活性是由激酶Dbf2促进的,并由PP2A酸酶Pph22抑制.
- 激活的Hmt1甲基化HnRNP,导致CLB2转录的稳定.
- Dbf2-介导的Hmt1激活是合作的,而Pph22脱化是分级的,允许敏感的调节.
- 营养饥饿和TOR抑制激活Pph22,导致CLB2耗尽和M相延迟.
结论:
- 通过Hmt1-介导的hNRNP甲基化确定了一种控制CLB2mRNA稳定的新型调节途径.
- Dbf2激酶和Pph22酸酶活动之间的平衡微调Hmt1功能,从而调节细胞循环的进展.
- 这种机制使酵母细胞能够适应M阶段的进入到营养的可用性,确保子细胞的活力.
- 这些发现提出了一个通用模型,其中Pph22活性调节环林mRNA稳定性,以将细胞循环进展与环境条件联系起来.
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