# Regulation of local translation in glia

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $531,206

## Abstract

ABSTRACT
To enable efficient specialization and dynamic regulation of subcellular regions, many cells have evolved local
translation of mRNA - yet the fundamental principles of such translation regulation in astrocytes are unknown.
Long studied in neurons, local translation of a variety of proteins is thought to be essential for the synapse-
specific changes that underlay learning and memory. In the prior cycle of this award we provided evidence
astrocytes also have a regulated local translation by using a variety of approaches. Here, we propose to continue
this work, focusing on the following question regarding this fascinating new basic biological phenomenon: what
is the regulatory grammar that determines when and which transcripts are locally translated in astrocytes?
Our central model is that elements in the untranslated regions (UTRs) of transcripts are responsible for their
enrichment or depletion from ribosomes in peripheral astrocyte processes (PAPs), via UTR interactions with
RNA binding proteins (RBPs) and microRNAs (miRNAs). However, with hundreds of potential elements to
screen, new, scalable methods are needed to systematically characterize how RNA localization and translation
is regulated in astrocytes, both at baseline and in response to signaling cues. Furthermore, glial morphology only
reaches full maturity in vivo, requiring in vivo functional studies. Therefore, we have developed a new method, a
synaptoneurosome–massively parallel reporter assay (SN-MPRA) which allows us to assess functional effects
of thousands of candidate UTR elements in vivo simultaneously. We will apply this to define the sequences that
modulate RNA localization in astrocytes. Furthermore, to better understand how a subset of these elements
function, we will define the role of a specific RBP, ‘quaking’ (QKI), in modulating local translation in astrocytes.
Finally, to understand how sets of transcripts might be regulated in a coordinated fashion for local translation,
we will examine the role of miRNA effector proteins (Ago2) along with specific miRNAs in regulating local
translation in astrocytes.

## Key facts

- **NIH application ID:** 10881925
- **Project number:** 5R01NS102272-07
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** JOSEPH D DOUGHERTY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $531,206
- **Award type:** 5
- **Project period:** 2017-05-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881925

## Citation

> US National Institutes of Health, RePORTER application 10881925, Regulation of local translation in glia (5R01NS102272-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10881925. Licensed CC0.

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