# When alternative splicing meets cytoskeleton organization, local translation, and transcription regulation

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $383,755

## Abstract

ABSTRACT / SUMMARY
Alternative splicing is an RNA processing mechanism that explains how single genes can produce more than
one transcript. Alternative splicing is a rule rather than an exception: in humans, more than 90% of genes
undergo alternative splicing, consistent with the increased cellular and functional complexity of higher
eukaryotes. Genome wide studies keep identifying multiple splice variants for thousands of genes but how they
differentially or similarly function in the cells is an arena that only few groups get into. The splicing field is heavily
focused on how alternative splicing is regulated for example by RBPs, transcription, or epigenetics components.
In contrast, how alternative splicing impacts protein function and physiology is a much less investigated area.
After our current NIGMS R01 ends, this MIRA/R35 will greatly help us keep building our research program in
this niche.
 Our lab is interested on how alternative splicing influences key cellular process such as membrane trafficking,
cytoskeleton dynamics, transcription, local translation, and phase separation in large, highly specialized cells
such as cardiomyocytes and myofibers. We are curious of how this interplay impacts organ physiology, and how
similar or different this is in other type of large, highly specialized cells such as neurons that exert very different
roles in our bodies. Our MIRA proposal will tackle this broad interest from three Angles, that are independent
from each other but at the same time will synergize our discoveries. Angle 1 will study how RNA processing
regulates cytoskeleton dynamics in skeletal muscle cells which are also highly mechanosensitive. This is
significant because muscle diseases caused by aberrant RNA processing show intracellular architecture and
mechanical defects. Angle 2 will examine the contribution of alternative splicing to phase separation and local
translation. This is significant because skeletal muscle cells are syncytial tubes with numerous nuclei that need
to coordinate transcription within nuclei and translation in their shared cytoplasm. Angle 3 will define the role of
splicing on regulating transcription. This is significant because transcription factors and chromatin regulators
control thousands of downstream programs that in turn drive cellular differentiation, cell fate, and tissue function.
Overall, our MIRA research will build mechanistic and physiological models of how RNA processing drives organ
development and tissue identity acquisition and maintenance.
 Finally, the MIRA format will give us flexibility to investigate our broad question and allow more time for: (a)
creativity, (b) thinking outside the box and at the frontiers of the field, (c) mentoring and training young scientists,
especially women and underrestended scholars, and (d) promoting diversity, inclusion, and equity in our field,
academia, and the society.

## Key facts

- **NIH application ID:** 10771637
- **Project number:** 1R35GM152426-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jimena Giudice
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $383,755
- **Award type:** 1
- **Project period:** 2024-07-09 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10771637

## Citation

> US National Institutes of Health, RePORTER application 10771637, When alternative splicing meets cytoskeleton organization, local translation, and transcription regulation (1R35GM152426-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10771637. Licensed CC0.

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