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

Lead Research Organisation: University of Birmingham
Department Name: Sch of Biosciences


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.

Technical Summary

Here we will establish in detail for the first time the biochemistry and protein dynamics of the ubiquitination-proteasome relay and its effects on meiotic recombination events in plants. We will use complementary genetic, molecular cytogenetic & protein biochemistry approaches to investigate the role of the ubiquitin proteasome system in regulating crossover (CO) determination and homologous recombination during plant meiosis, in a conserved process we have called Meiosis Associated Degradation (MEIAD). We will: i) functionally characterise the key proteolytic components involved (including the E3 ubiquitin ligase HEI10, other putative E3s, the AAA-type ATPase CDC48A and the 26S proteasome), ii) identify their direct meiotic degradation targets, iii) define their synergistic & spatiotemporal activity at chromosome-axes during meiotic progression and CO establishment, iv) investigate how pharmacological and genetic manipulation of MEIAD modulates meiosis (in particular, CO number and localisation), and v) explore how changes in temperature during meiosis could affect meiotic recombination outcomes through changes in MEIAD. In doing so, this work will uncover how two major cellular processes - recombination & proteasomal degradation - interact to influence genetic inheritance in plants, providing a framework for understanding this critical process that could be targeted for manipulating recombination in diverse species. This knowledge could lead to real agronomic benefit through increasing the capacity for generating genetic variation in economically important crops.


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