# mRNA assembly in Drosophila germ granules

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2022 · $409,375

## Abstract

mRNA ASSEMBLY IN DROSOPHILA GERM GRANULES
Development of every species relies critically on spatially organized messenger RNAs (mRNAs). Indeed, even a
single asymmetrically distributed mRNA can specify the morphology of cells, the body plan of a developing
organism and cell lineages across metazoans. RNA binding proteins (RBPs) typically organize mRNAs and
recruit them to subcellular structures. However, mRNAs can also self-organize into multi-mRNA assemblies
independently of other cellular components. mRNA assemblies are found in healthy cells in different species
and are often associated with RNA granules, membraneless ribonucleoprotein (RNP) particles that regulate
translation and stability of mRNAs. mRNA assemblies are also a hallmark of pathogenesis in human repeat
expansion disorders such as myotonic dystrophy 1 (MD1), amyotrophic lateral sclerosis (ALS) and
spinocerebellar ataxia (SCA). These findings indicate that mRNA assembly is an inherent property of an mRNA
that could be biologically relevant. However, the exact mechanism and potential biological functions of mRNA
assembly is unclear. mRNAs have been shown to self-assemble by phase separation, a process akin to oil-and-
water de-mixing. Here, RNA:RNA interactions, which promote intermolecular (trans) base-pairing and
secondary (cis) RNA structures have been implicated in driving mRNA assembly. In addition, in vitro data
suggest that RNA helicases, which are core constituents of RNA granules are thought to dissolve RNA:RNA
interactions in granules. In light of these findings, several critical questions arise. How do mRNAs
self-assemble in granules designed to prevent RNA:RNA interactions? What is the role of mRNA assemblies in
RNA granules? What is the function of trans and cis RNA:RNA interactions and RNA helicases in the
formation and function of mRNA assemblies and RNA granules? The five-year goal of this study is to
answer these questions and determine the mechanism and biological function of mRNA
assembly in Drosophila germ granules. mRNA assemblies tend to form as small clusters that are acutely
sensitive to the concentration and the environment in which they form. Thus, the central challenge in
studying mRNA assembly is that methods must be employed that enable examination of this process in
vivo and with high resolution and sensitivity. We will use genetic and quantitative, super-resolution
imaging approaches to analyze mRNA assembly in intact cells and within their natural cellular
context. We aim to uncover new insight into how organisms harness mRNA assemblies to promote
development and how misregulation of mRNA assembly could contribute to human diseases, such as MD1,
ALS and SCA.

## Key facts

- **NIH application ID:** 10468879
- **Project number:** 5R35GM142737-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Tatjana Trcek
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $409,375
- **Award type:** 5
- **Project period:** 2021-08-12 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468879

## Citation

> US National Institutes of Health, RePORTER application 10468879, mRNA assembly in Drosophila germ granules (5R35GM142737-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10468879. Licensed CC0.

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