# Novel Regulatory Mechanisms of Drosophila Pumilio

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2022 · $321,207

## Abstract

PROJECT SUMMARY
 The long term goal of our research is to determine how gene expression is regulated at the post-
transcriptional level. Control of messenger RNA (mRNA) translation and degradation underlies important
biological processes including development, fertility and neurological functions. The proposed work focuses on
the archetypal mRNA regulator, Drosophila Pumilio (Pum), which belongs to a family of RNA-binding proteins
that are conserved throughout eukarya. Pum binds an extensive group of mRNAs including those that encode
key developmental morphogens. Upon binding to an mRNA, Pum represses expression of the encoded
protein. We find that Pum accelerates decay of the target mRNA and the proposed research seeks to discover
the mechanism of Pum-mediated mRNA degradation. We developed novel assays to measure Pum activity in
Drosophila cells and discovered multiple unique Repression Domains that potently repress target mRNAs. In
preliminary work, we identified key co-repressors that are necessary for Pum repression. In the first aim, we
measure the impact of the Repression Domains on protein expression and mRNA degradation and interrogate
the functional roles of two classes of mRNA decay factors in repression by each Pum Repression Domain. We
interrogate the physical interactions of the co-repressors with each Pum Repression Domain and measure
their recruitment to Pum-regulated target mRNAs. In the second aim, we investigate the role of each Pum
Repression Domain in embryonic development and proper spatial and temporal control of gene expression
during early development. This research will reveal novel mechanisms of Pum repression. The resulting
discoveries are expected to broadly enhance our understanding of post-transcriptional control and specifically
improve knowledge of gene regulation in development, fertility, stem cell proliferation, and the nervous system.

## Key facts

- **NIH application ID:** 10312121
- **Project number:** 5R01GM105707-10
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Aaron Charles Goldstrohm
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $321,207
- **Award type:** 5
- **Project period:** 2013-09-20 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312121

## Citation

> US National Institutes of Health, RePORTER application 10312121, Novel Regulatory Mechanisms of Drosophila Pumilio (5R01GM105707-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10312121. Licensed CC0.

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