# Axonal Transport of mRNA for Mitochondrial Proteins (Diversity Supplement)

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $64,167

## Abstract

SUMMARY
Neurons use local translation to preserve the health of axons, dendrites, and synapses that are far from the
soma. Local translation allows them to respond to local needs. While studying the local synthesis of PINK1 in
axons and dendrites, we discovered that the PINK1 mRNA was transported into axons and dendrites by
“hitchhiking” on mitochondria. The association of the PINK1 mRNA with mitochondria was mediated by
synaptojanin2 and synaptojanin2 binding protein (SYNJ2BP). Synaptojanin2, like synaptojanin1, is an inositol
lipid phosphatase, but also contains a predicted RNA-Recognition Motif (RRM); mutation of the RRM in
synaptojanin2 prevents its ability to localize the PINK1 transcript to mitochondria. We know that synaptojanin2
can bind additional mRNA species, not just PINK1, including many for mitochondrial proteins. Thus
synaptojanin2 represents an important addition to the roster of mechanisms that can transport neuronal
mRNA. We therefore propose to study the broad significance of the synaptojanin2/SYNJ2BP mechanism for
mRNA transport in neurons and for the function of neuronal mitochondria. To this end, we have made both
mouse and human iPSC lines with mutations in the RRM of synaptojanin2 (SYNJAAA). In AIM 1 we will catalog
the neuronal mRNA species bound to the RRM of synaptojanin2 and determine the extent to which it is
required for their transport into axons and dendrites. In AIM 2 we will catalog the mRNA present on neuronal
mitochondria. We will determine to what extent synaptojanin2 and SYNJ2BP are needed for this localization.
We will also catalog the mRNA species present in synaptosomes from control and SYNJAAA mice to determine
which presynaptic mRNAs require binding to synaptojanin2 to reach the synapse. In AIM3 we examine the
functional consequences of mutations in the RRM of synaptojanin2 for the protein content of synapses. the
morphology and functioning of neuronal mitochondria, and the health and survival of neurons.

## Key facts

- **NIH application ID:** 11088466
- **Project number:** 3R01NS107490-06A1S1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Thomas L. Schwarz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $64,167
- **Award type:** 3
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11088466

## Citation

> US National Institutes of Health, RePORTER application 11088466, Axonal Transport of mRNA for Mitochondrial Proteins (Diversity Supplement) (3R01NS107490-06A1S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11088466. Licensed CC0.

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