# Muscleblind facilitates kinesin dependent RNA localization in neurons

> **NIH NIH F31** · EMORY UNIVERSITY · 2020 · $45,520

## Abstract

PROJECT SUMMARY/ABSTRACT
RNA localization and local protein synthesis enable highly differentiated, post-mitotic cells, such as neurons, to
respond to external perturbations and adjust protein levels in specialized compartments in a timely and efficient
manner. Proper RNA localization and local translation are necessary for neuronal functions that underlie learning
and memory. Myotonic Dystrophy Type 1 (DM1), which affects 1 in 8000 worldwide, is an example of disease in
which RNA mislocalization may contribute to disease progression. While the muscular symptoms of DM1 have
been thoroughly studied, DM1 patients also present with multiple debilitating CNS symptoms, such as
hypersomnia, anhedonia, and neurocognitive/behavioral disorders. It is critical to elucidate the basic mechanism
of RNA localization in healthy neurons to better understand the CNS symptoms associated with a disease
involving RNA mislocalization, such as DM1. In this proposed project, we plan to utilize a multi-faceted approach
that combines multiple imaging and biochemical techniques. Primary cortical neurons from wild type mouse
embryonic brains will serve as our principal model. The Bassell Lab has extensive background in studying RNA
biology and has published extensively on the roles of the RNA-Binding Proteins (RBPs) Fragile X Mental
Retardation (FMRP) and Survival of Motor Neuron (SMN) proteins which are also affected in related neurological
diseases. The goal of this project is to elucidate the role that a specific RBP implicated in DM1 pathogenesis,
Muscleblind (MBNL), has as a facilitator of mRNA localization from the cell body to pre-synaptic compartments.
We hypothesize that MBNL acts an adaptor between its mRNA cargo and specific kinesin motor proteins (Kifs).
Kinesin was chosen over other motor proteins as the focus of this proposal because it is well-established that
kinesins facilitate the long distance anterograde movement of the cellular cargo away from the soma. Another
goal of this project is to identify the specific Kifs that interact with MBNL to transport target mRNA transcripts to
proper destinations within neurons. Depending on the cargo and destination, certain Kifs or combinations of Kifs
might necessary for proper transportation. This work will strengthen our understanding of RNA localization and
the role that RBPs play in this process. This research will also motivate future studies to identify various
components of RNA transport granules, necessary not only for localization, but also granule formation,
anchoring, and disassembly. The knowledge gained from this project could be applied to pathological conditions
that arise due to RNA mislocalization, such as DM1.

## Key facts

- **NIH application ID:** 10156958
- **Project number:** 1F31NS117086-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Luke Andrew Knudson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-09-21 → 2023-07-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156958

## Citation

> US National Institutes of Health, RePORTER application 10156958, Muscleblind facilitates kinesin dependent RNA localization in neurons (1F31NS117086-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10156958. Licensed CC0.

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