# Structure to phenotype analysis of a conserved RNA binding protein required for reproduction

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $512,242

## Abstract

During metazoan development, polarization of the body axes is of critical importance, as asymmetric
cell division initiates cell specialization pathways. A family of conserved RNA-binding proteins
characterized by CCCH-type tandem zinc finger (TZF) domains is required for axis polarization and
cell type specification in the early embryo of C. elegans. A cascade of events essential to the oocyte-
to-embryo transition is initiated by two members of this family, OMA-1/2. The process initiates with
OMA-1/2 turnover and culminates with asymmetric segregation of cellular components to opposing
poles of the embryo. Mutation of OMA-1/2 blocks oocyte maturation and prevents fertilization. We
have observed that OMA-1 binds RNA with relatively low specificity in vitro, but regulates specific
mRNAs in vivo. We have also determined that OMA-1 RNA binding is highly cooperative, a feature
never before observed in a protein from the CCCH-type TZF family. Our goal is to investigate OMA-
1/2 activity from structure to phenotype. We will determine the molecular mechanism or RNA-binding
cooperativity using NMR spectroscopy, computer simulations, and quantitative biochemistry. We will
also define how RNA-binding cooperativity defines OMA-1 biological activity in worms. We will
determine which mRNAs are regulated by OMA-1/2 in oocytes and of these mRNAs which are the
most critical to reproduction. This research will lead to a new understanding of how the molecular
properties of OMA-1 determine its function in reproductive biology in living animals.

## Key facts

- **NIH application ID:** 10072181
- **Project number:** 1R01GM139316-01
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Francesca Massi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $512,242
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072181

## Citation

> US National Institutes of Health, RePORTER application 10072181, Structure to phenotype analysis of a conserved RNA binding protein required for reproduction (1R01GM139316-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10072181. Licensed CC0.

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