# Mechanistic dissection of a novel meiotic exit regulation by autophagy

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $342,825

## Abstract

PROJECT SUMMARY
 Targeted proteolysis is essential for regulating meiosis, the specialized program that produces haploid
gametes from diploid progenitor cells. Although the role of the ubiquitin/proteasome system in meiosis has
been well-described, the potential of autophagy to mediate distinct steps during the meiotic divisions
remains unexplored.
 My laboratory recently made the novel discovery that autophagy, a conserved pathway to lysosomal
degradation, is essential for faithful meiotic chromosome segregation and meiosis completion in budding
yeast. We further identified a major target of this meiotic autophagy activity — Rim4, a meiosis-specific RNA
binding protein (RBP) that adapts an amyloid-like state and sequesters mRNAs encoding specific proteins
involved in meiotic regulation, chromosome segregation and sporulation (cytokinesis). Importantly, during
meiotic and early embryotic cell development, gene expression is primarily regulated post-transcriptionally
using maternal mRNAs that are selectively bound by RBPs. The temporal translation of meiotic proteins,
which control meiotic cell progression, is regulated by these RBPs through largely unknown and varied
mechanisms [10]. Our finding reveals a novel link between autophagy and meiotic translation. In
addition, we discovered that autophagy degrades a set of proteins that are associated with spindle pole body
(SPB, the yeast centrosome) structure and function, which is essential for both meiosis and sporulation. We
propose that autophagic degradation of specific proteins, e.g. Rim4 amyloid-like aggregates, Spc42
and Spo74, at multiple meiotic stages contributes to meiosis-programed translational control and
meiosis-coupled SPB dynamics. These novel roles of selective autophagy converge to coordinate meiosis
and sporulation.
 The major goals of this proposal are (1) to mechanistically dissect how autophagy regulates Rim4
degradation and what effects this has on meiotic gene expression of Rim4 mRNA targets; and (2) to reveal the
role of meiotic autophagy in restraining the number of SPB per cell. Such understanding will reveal new principles
underlying mRNA-specific translational control and meiotic regulation and, if autophagy is involved in human
meiosis as well, inform strategies for prevention of chromosomal disorders, e.g. Turner syndrome (monosomy
X, frequency: 1/2,500 newborn girls) [11] and Down syndrome (trisomy 21, frequency: 1/800 newborns) [12].
This study will also shed light on the design of therapeutics to clear deleterious amyloid-like aggregates
associated with neurodegeneration (e.g. amyloid beta in Alzheimer’s disease). This grant proposes to: (1)
Elucidate how autophagy promotes Rim4 degradation to regulate meiotic translation; and (2) Investigate
how autophagy regulates yeast centrosome dynamics during meiosis.

## Key facts

- **NIH application ID:** 9968779
- **Project number:** 1R01GM133899-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** fei wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $342,825
- **Award type:** 1
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968779

## Citation

> US National Institutes of Health, RePORTER application 9968779, Mechanistic dissection of a novel meiotic exit regulation by autophagy (1R01GM133899-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9968779. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*