# Mechanisms of mRNA localization and translational control in Drosophila development

> **NIH NIH R35** · PRINCETON UNIVERSITY · 2024 · $702,853

## Abstract

PROJECT SUMMARY
Our long-term goal is to understand post-transcriptional mechanisms that spatially and temporally control gene
activity during animal development. We focus on intracellular mRNA localization, translational control, and
degradation, which play crucial roles in regulating production of proteins from maternally supplied transcripts.
These transcripts, which underpin the initial developmental program of nearly all animals, are pre-loaded in the
egg. Thus, control over where and when they are deployed to produce protein must be exerted post-
transcriptionally. Our research capitalizes on the highly manipulable Drosophila model, which relies heavily on
maternal transcripts, to investigate mechanisms that generate asymmetric maternal mRNA and protein
distributions needed for embryonic body patterning and germline development. Our previous work revealed that
numerous mRNAs accumulate at the posterior of the Drosophila oocyte through their incorporation into large,
non-membrane-bound ribonucleoprotein (RNP) assemblies called germ granules. During embryogenesis, germ
granules deliver this cohort of mRNAs to the primordial germ cells, where they support germline development.
Germ granules are a hallmark of primordial germ cells throughout the animal kingdom. They contain conserved
components that indicate a common function in RNA regulation to promote the differentiation, proliferation, and
maintenance of the germline. Germ granules are just one of a plethora of cellular RNP assemblies that have
been characterized for their phase-transitioned behavior. How mRNA regulation occurs in the context of RNA
granules more generally and its biological significance remain, however, poorly understood. As complex and
biologically relevant RNP assemblies, germ granules are ideal for studying RNA localization, translational
control, and degradation and, in particular, their biological significance. Our studies lead to a model for germ
granule "client" RNA accumulation by self-recruitment and organization into homotypic clusters. This model
provides a framework to investigate how mRNAs self-organize in granules and how this organization imparts
selective control over the translation and stability of different mRNAs within shared granules. We will combine
quantitative high resolution imaging with powerful biochemical and genetic/genomic strategies, as well as novel
methods that disrupt granules, to investigate fundamental principles governing the organization of granule client
RNAs. These studies will enable us to decipher the relationship between granule association, translational
activity, and germ granule function. Given the widespread use of post-transcriptional mechanisms during
development, and the prevalence of RNA compartmentalization in granules, this work will have broad impact.
Mechanistic insights gained from our studies will also provide a foundation for understanding defects in RNA
metabolism associated with numerous disorders including infert...

## Key facts

- **NIH application ID:** 10825567
- **Project number:** 5R35GM126967-07
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** ELIZABETH R GAVIS
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $702,853
- **Award type:** 5
- **Project period:** 2018-04-15 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825567

## Citation

> US National Institutes of Health, RePORTER application 10825567, Mechanisms of mRNA localization and translational control in Drosophila development (5R35GM126967-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10825567. Licensed CC0.

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