# Ribonucleoprotein Biogenesis and Epigenetic Gene Regulation

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $652,325

## Abstract

Abstract
The research in our laboratory centers on foundational mechanisms that regulate eukaryotic gene expression.
In particular, we are interested in roles played by small nuclear ribonucleoproteins (RNPs) and histone post-
translational modifications (PTMs) in the transmission of genetic and epigenetic information required for proper
metazoan development and genome function. We have developed innovative model systems in Drosophila
melanogaster to study gene regulation and neuromuscular disease. Critically, these models allow direct
interrogation of specific residues present within conserved genes and multi-gene families. For example, we can
now study the biological function of a specific histone PTM by changing the acceptor residue to an amino acid
that cannot be appropriately modified and then replacing all wild-type copies of a given histone gene with mutant
copies. This approach is not possible in other animal models. Hence, for the first time in any multicellular
eukaryote, we can now directly determine the extent to which a given histone PTM contributes to cell fate and
organismal development. Similarly, we generated an allelic series of animals that express missense mutations
in the Survival Motor Neuron (SMN) gene that are derived from human Spinal Muscular Atrophy (SMA) patients.
This series represents the largest number of SMA-causing point mutants currently available in any model
organism. Several of these alleles serve as separation-of-function mutations that uncouple the putative
housekeeping and tissue-specific activities of SMN, enabling us to study these processes independently. We
employ genome-wide techniques together with molecular genetics and biochemistry to identify cellular pathways
and binding partners that are dysregulated in human cancer and neuromuscular disease. Using these two
powerful genetic platforms, we expect to identify factors and mechanisms that enable a specific chromatin mark
to modulate the expression of an individual transcript or an entire chromosome, as well as those that carry out
the assembly and maturation of spliceosomal and messenger RNPs.

## Key facts

- **NIH application ID:** 10828829
- **Project number:** 5R35GM136435-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** A. Gregory Matera
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $652,325
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828829

## Citation

> US National Institutes of Health, RePORTER application 10828829, Ribonucleoprotein Biogenesis and Epigenetic Gene Regulation (5R35GM136435-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10828829. Licensed CC0.

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