# Mechanism of mRNA Localization and Localized Translation in Neurons

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $745,972

## Abstract

ABSTRACT
The neuron is the basic cellular unit of the brain. For neurons to work properly, they must
be plastic and constantly capable of changing in response to stimuli, forming and
stabilizing new connections. This process requires proteins to be added to the new
synaptic contact, and this in turn results from the targeting of mRNA to these sites of
activity. This is the mechanistic basis of learning and memory since the synapse is
stabilized by the production of proteins in response to stimulation that are important for
its structural integrity. How this mRNA is regulated in neurons to make the right protein
at the right place and time has been the subject of our investigations over the years of
this funding. This proposal exploits the tools we generated during the last funding period
to address how mRNA is regulated in dendrites. One of these tools is a mouse where we
have tagged the β-actin gene with a fluorescent marker to follow individual mRNAs in
live neurons. We have found that the mRNA is encased in an inert form as it travels
around in the dendrite. When it comes into the proximity of a stimulated dendritic spine,
it unfurls its RNA payload and makes a burst of protein, but then returns to a dormant
state after 16 minutes. The mRNA sits at the place where it was last stimulated for
hours, awaiting the next signal, wherein it will initiate another round of proteins. In this
way, the synaptic contact is built up, consistent with a learning and memory paradigm
that relies on repetitive stimulation. If there are no further activating signals, the mRNA
continues its search, moving in short processive movements broken by periods of
diffusion. The current proposal follows up on the discovery of the particular protein that
binds to the mRNA zipcode responsible for directing it to its site (zipcode binding protein,
ZBP1), anchors the mRNA at the site of stimulation. The model we have constructed
suggests that the mRNA translates upon a further stimulation and we intend to focus on
this point of regulation by describing the kinetics of these events and the proteins that
play a role in these events. Up to this point we have investigated β-actin mRNA because
actin is the major structural protein in cells, and in the synapse as well. However the
regulatory mechanism leading to a complex structure such as a synapse must
orchestrate the expression of many proteins. For this reason, we have constructed
another mouse with an mRNA important for learning, Arc, that has been tagged with a
different fluorescent marker. In this proposal, we will characterize the mRNAs for β-actin
and Arc in mice together where both mRNAs are individually detectable by different
colored fluorochromes. We propose eventually a third hybrid-color mRNA for CaMKIIα,
an essential protein in synapses. Our goal is to uncover the mechanisms that govern the
regulation of different mRNAs in response to stimulatory activations of the neuron: the
timing of their synthesis, localization ...

## Key facts

- **NIH application ID:** 9993929
- **Project number:** 5R01NS083085-28
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Carolina Ines Eliscovich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $745,972
- **Award type:** 5
- **Project period:** 1992-03-03 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993929

## Citation

> US National Institutes of Health, RePORTER application 9993929, Mechanism of mRNA Localization and Localized Translation in Neurons (5R01NS083085-28). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9993929. Licensed CC0.

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