# Mechanisms of mRNA localization and translational control in Drosophila development

> **NIH NIH R35** · PRINCETON UNIVERSITY · 2022 · $620,445

## Abstract

PROJECT SUMMARY
Our long-term research goal is to understand post-transcriptional mechanisms that control gene activity during
early animal development. We focus on intracellular mRNA localization and translational control, which play
crucial roles in regulating the production of proteins from maternally supplied transcripts. Because these
transcripts, which control the initial developmental program of nearly all animals, are pre-loaded in the egg, the
spatial and temporal expression of the proteins they encode must be exerted post-transcriptionally. In animals
as diverse as flies and frogs, mRNA localization and local control of translation produce asymmetric protein
distributions required for axis formation, patterning, and germline development. Often many different transcripts
must be localized concurrently to various subcellular locations. Additionally, translational control must be
superimposed to repress unlocalized transcripts and activate properly localized transcripts. How specificity is
conferred on these processes, so that each transcript is targeted to its correct destination and translated
appropriately, is poorly understood. Our research has capitalized on the Drosophila egg, which relies heavily
on maternal transcripts, to investigate mechanisms of mRNA localization and its coupling to translational
control. Our early studies focusing on nanos mRNA led to the discovery of a diffusion-and-entrapment
mechanism used by numerous transcripts for localization to the specialized germ plasm at the posterior of the
oocyte. Produced by the ovarian nurse cells and then transferred to the oocyte, these transcripts are co-
packaged at the posterior end into ribonucleoprotein complexes (RNPs) called germ granules. Later during
embryogenesis, germ granule mRNAs are segregated as a cohort to the primordial germ cells, where they are
required for germline development. Despite their shared dependence on germ granule localization tor
translational activation, different transcripts have distinct temporal demands. Our recent studies have led to a
stepwise model for germ granule assembly that provides a framework for understanding the composition,
structure, and translational properties of RNPs and their functions. Determining the specific roles of shared and
RNA-specific proteins in controlling RNP assembly and translation will, in turn, be fundamental to a deeper
understanding of mRNA localization as a mechanism for generating protein – and consequently cellular –
asymmetries. To elucidate how localized assembly and function of complex RNA granules is controlled, we will
take advantage of quantitative high resolution imaging, in vivo fluorescent RNA labeling, and new biochemical
strategies to identify cis-acting regulatory elements and interacting proteins that mediate both individualistic
and coordinate RNA behaviors. Ribosome footprinting, a genome-level approach for monitoring translation, will
be employed to investigate mechanisms that impose tran...

## Key facts

- **NIH application ID:** 10377348
- **Project number:** 5R35GM126967-05
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** ELIZABETH R GAVIS
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $620,445
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377348

## Citation

> US National Institutes of Health, RePORTER application 10377348, Mechanisms of mRNA localization and translational control in Drosophila development (5R35GM126967-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10377348. Licensed CC0.

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