# Coordinating different steps in mRNA localization

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $313,000

## Abstract

Expression of proteins in spatially restricted patterns frequently relies on prior localization of the encoding
mRNAs. One conserved RNA transport mechanism, used in multiple cell types, involves a stem-loop
transport signal within the mRNA, and proteins (Egalitarian and Bicaudal-D) to bind the signal and link the
RNA cargo with the dynein motor for transit along microtubules. This transport system also anchors the
mRNAs at their destination, although anchoring is poorly understood. The initial step in localization of
Drosophila oskar mRNA - transport from the nurse cells to the oocyte - relies on this conserved transport
system. However, oskar mRNA differs from simple examples of this system, in that the mRNA must then be
transferred to a different localization machinery for a later step in localization. Notably, the cis-acting
localization signals in oskar mRNA that direct the initial transport step are individually weak, even though
transport is robust. Replacing the multiple weak signals with a single strong signal disrupts the later step in
localization. This suggests that weak association with the machinery for the initial transport step allows the
mRNA to be handed off to the other type of machinery. A model is proposed to explain what makes the
oskar transport signals weak, and how the conflicting requirements for weak signals yet highly efficient
transport can both be met. In part, this model relies on Staufen protein to inhibit association of the oocyte
transport machinery with the oskar oocyte transport signals. Staufen is more conventionally thought to act in
the later step of oskar mRNA localization, although the staufen mutant phenotype is equally consistent with
both models. One Aim is to confirm, using an affinity purification approach, that oskar relies on the
conserved transport system for its initial step of localization and to reveal candidates for other contributing
factors. The second Aim is to test two predictions of what makes the individual transport signals weak:
modest affinity for the recognition factor, Egalitarian; and displacement of Egalitarian by Staufen after the
mRNA arrives in the oocyte. The third Aim is to ask if the contribution of Staufen to localization of oskar
mRNA is limited to the novel role postulated here, or if Staufen also has the conventional role, or both. The
novel role for Staufen could explain how it contributes to a wide variety of forms of post-transcriptional
regulation, a possibility that will be tested. A final Aim is to exploit unique features of this system in a
sensitized genetic assay to evaluate candidate transport/anchoring factors, and to screen for such factors.
Further analysis of these factors should provide substantial insights into many aspects of mRNA localization
and anchoring.

## Key facts

- **NIH application ID:** 10001543
- **Project number:** 5R01GM124345-04
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Paul M. Macdonald
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $313,000
- **Award type:** 5
- **Project period:** 2017-09-07 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001543

## Citation

> US National Institutes of Health, RePORTER application 10001543, Coordinating different steps in mRNA localization (5R01GM124345-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001543. Licensed CC0.

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