MEIAD: Investigating roles for Meiosis Associated Degradation during meiotic recombination in plants

MEIAD：研究植物减数分裂重组过程中减数分裂相关降解的作用

• 批准号: BB/Y002512/1
• 负责人: Eugenio Sanchez-Moran
• 金额: $ 104.59万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY002512%2F1
• 关键词: MEIAD; Investigating; roles; Meiosis; Associated

Meiosis is the process where a single cell divides twice to produce four gametes containing half the original amount of genetic information. During this process, meiotic recombination occurs, generating crossovers (COs) that are the main drivers of genetic variation in plants, which is crucial for plant breeding. Despite their importance, COs are unevenly distributed across the genome, particularly in large-genome crops, in which they are mostly localized near chromosome ends. Such CO distribution patterns significantly limit the genetic variation generated in each meiotic division. It is therefore critical to understand the mechanistic basis of CO formation and distribution, if we are to identify new ways of manipulating this process for the benefit of crop improvement.The stability and half-lives of proteins in cells can vary widely, and tight control of where and when proteins are degraded is critical for accurately regulating most cellular processes. The major pathway of selective protein degradation in plant cells is the ubiquitin-proteasome system (UPS). Here, a small molecule called ubiquitin is added to target proteins by specific enzymes called E3 ligases, which triggers their rapid degradation by a large complex called the 26S proteasome. Meiotic recombination has previously been shown to depend on some components of the UPS (for example, the E3 ligase HEI10) but the underlying mechanisms and function of these components in plants are yet to be fully investigated. In particular, the meiotic ubiquitination targets of the UPS are currently unknown, leaving a key gap in our knowledge of how regulated protein degradation coordinates recombination. In this proposal, we will use complementary genetic, molecular cytogenetic, and protein biochemistry approaches to identify and investigate the role of the UPS in regulating meiotic recombination in plants, in a conserved process we have called Meiosis Associated Degradation (MEIAD). We will use our combined skills in molecular cytogenetics and protein biochemistry to functionally characterise roles for diverse UPS components in coordinating meiotic recombination and progression, paying particular attention to identifying direct meiotic ubiquitination targets. In doing so, this work will uncover how two major cellular processes interact to influence genetic inheritance in plants: meiotic recombination and proteasomal degradation. This will provide a framework for understanding this critical process that could be targeted to manipulate recombination and increase genetic variation in diverse crop species.

减数分裂是一个细胞分裂两次产生四个配子的过程，其中包含的遗传信息是原始数量的一半。在这个过程中，减数分裂重组发生，产生杂交（COs），这是植物遗传变异的主要驱动因素，对植物育种至关重要。尽管它们很重要，但COs在整个基因组中的分布并不均匀，特别是在大基因组作物中，它们大多定位在染色体末端附近。这种CO分布模式极大地限制了每次减数分裂产生的遗传变异。因此，了解CO形成和分布的机制基础是至关重要的，如果我们要确定操纵这一过程的新方法，以有利于作物改良。细胞中蛋白质的稳定性和半衰期变化很大，严格控制蛋白质降解的地点和时间对于精确调节大多数细胞过程至关重要。植物细胞中选择性蛋白降解的主要途径是泛素-蛋白酶体系统（UPS）。在这里，一种叫做泛素的小分子被一种叫做E3连接酶的特殊酶添加到目标蛋白质上，这种酶被一种叫做26S蛋白酶体的大复合体触发它们的快速降解。减数分裂重组先前已被证明依赖于UPS的一些成分（例如E3连接酶he10），但这些成分在植物中的潜在机制和功能尚未得到充分研究。特别是，UPS的减数分裂泛素化目标目前尚不清楚，这在我们如何调节蛋白质降解协调重组的知识中留下了一个关键空白。在这篇论文中，我们将使用互补的遗传学、分子细胞遗传学和蛋白质生物化学方法来鉴定和研究UPS在调节植物减数分裂重组中的作用，这一保守的过程被我们称为减数分裂相关降解（MEIAD）。我们将利用我们在分子细胞遗传学和蛋白质生物化学方面的综合技能，从功能上表征各种UPS组件在协调减数分裂重组和进展中的作用，特别注意识别减数分裂泛素化的直接目标。这样，这项工作将揭示两个主要的细胞过程如何相互作用来影响植物的遗传：减数分裂重组和蛋白酶体降解。这将为理解这一关键过程提供一个框架，可以有针对性地操纵重组和增加不同作物物种的遗传变异。