通过酵母拼接因子Fyv6控制3'拼接地点的选择
Katherine A Senn1, Karli A Lipinski2, Natalie J Zeps1
1Department of Biochemistry, University of Wisconsin-Madison, Madison, United States.
eLife
|December 17, 2024
概括
蛋白质Fyv6 (FAM192A) 通过确保正确的3'拼接位选择来调节mRNA拼接. 丢失Fyv6导致广泛的替代拼接事件,影响基因表达.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 结构生物学 结构生物学
背景情况:
- 预mRNA拼接是基因表达的关键过程,发生在两个不同的步骤:5'拼接部位 (SS) 分裂和外因子结合.
- 特定的蛋白质因子暂时与结合酶体结合,以调节这些步骤,被归类为第一或第二步因子.
- Fyv6 (FAM192A) 之前被确定为酵母中的第二步因子,但其更广泛的转录基因影响仍然不清楚.
研究的目的:
- 为了研究Fyv6对mRNA拼接的全基因组影响.
- 阐明Fyv6影响拼接精度的分子机制.
- 了解Fyv6在结合体内功能的结构基础.
主要方法:
- 使用RNA测序 (RNA-seq) 分析了缺乏Fyv6.6的酵母中的拼接变化.
- 使用高分辨率冷电子显微镜 (cryo-EM) 来确定含有Fyv6.6的酵母结合体的结构.
- 进行了基因查,以确定Fyv6删除的抑制突变.
主要成果:
- Fyv6的损失导致了跨转录组的非共识,分支点 (BP) 邻近3'SS的激活.
- 冷-EM结构显示Fyv6是唯一与Prp22 ATPase相互作用的第二步因子,与第一步因子Yju2.2相互排斥的结合.
- 结构和遗传分析确定了Fyv6的功能域,并提供了对其在结合体动力学中的作用的见解.
结论:
- Fyv6在促进共识的使用中发挥着关键作用,分支点 (BP) 距离3' SS在拼接过程中.
- 建议Yju2和Fyv6的交换以促进高效的外链结合.
- Fyv6的功能对于保持拼接保真性和防止异常拼接事件至关重要.
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