# A ribosome interactome that regulates local translation and neural function

> **NIH NIH R21** · STANFORD UNIVERSITY · 2023 · $196,750

## Abstract

A central question in cell biology is how gene expression is spatially and temporally regulated in response to
stimuli. Neurons are particularly mystifying due to their complex morphology, wherein dendrites and axons that
comprise most of the cell volume extend great distances (>10 mm in length) from the cell body. Paradoxically,
neurons must respond in a fast and selective manner to accurately transmit synaptic signals across these
distances to neighboring cells. In vivo genetic studies have demonstrated a clear requirement for newly
synthesized proteins to drive long-term potentiation and depression, synaptic plasticity, and memory formation
Indeed, all the components necessary for translation including mRNAs, ribosomes, and initiation factors, are
localized within axons and dendrites. This raises the question: how are specific subsets of mRNAs
translationally regulated in a selective, fast, and spatially localized manner to propagate distinct signals within
neurons? Intriguingly, trans-acting factors known as ribosome-associated proteins (RAPs) have emerged as
critical players in regulating translational specificity and subcellular localization that can rapidly fine-tune
translation in response to extracellular signals. However, we lack the technologies to be able to precisely
isolate and analyze the translational machinery at discrete locations within neurons. In this grant, we will apply
new technologies to mark and characterize ribosomes in distinct subdomains of neurons for the first time. We
will also directly delineate how RAP binding to the ribosome endows greater specificity in translational control
to reflect unique cellular needs and diversity in subcellular space in neurons. In Aim1 we will develop a new
technology known as ALIBi (AviTag-specific Location-restricted Inducible Biotinylation), which enables
proximity-dependent biotin labeling for the isolation of ribosomes in a spatiotemporally targeted
manner. With this technology we will be able to identify RAPs and study localized translation at an
unprecedented subcellular resolution in a tunable and highly specific fashion. In Aim2 we will characterize a
novel RAP that encodes an ATP-dependent helicase that is present on neuronal ribosomes. Neurons translate
some of the longest transcripts in the body containing highly structured 5’UTRs that may require helicase
activity for their translation. Here, we will address the outstanding question of whether RAP binding to neural
ribosomes endows greater specificity to translational control. Together, this work will uncover the functional
consequences of RAP-ribosome interactions with respect to localized translation and neural development
utilizing new technologies that for the first time enable us to directly probe neural ribosomes and their functions
in localized translational control.

## Key facts

- **NIH application ID:** 10632135
- **Project number:** 5R21MH130323-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Maria Barna
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $196,750
- **Award type:** 5
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10632135

## Citation

> US National Institutes of Health, RePORTER application 10632135, A ribosome interactome that regulates local translation and neural function (5R21MH130323-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10632135. Licensed CC0.

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