# Mechanisms of messenger RNA splicing and RNA processing regulation

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $393,750

## Abstract

PROJECT SUMMARY
 Messenger RNA splicing is carried out by a large macromolecular machine, the spliceosome,
which undergoes dramatic rearrangements as it assembles onto a pre-messenger RNA. Our
understanding of this elegant ribonucleoprotein machine has advanced significantly with the
availability of cryoEM structures and an extensive “parts list” of splicing components. However, many
questions remain about how spliceosome assembly takes place in the cell, where the spliceosome
machinery assembles onto a nascent transcript that is being actively transcribed from a chromatin
template, i.e. co-transcriptionally. Moreover, assembly of the spliceosome and splicing catalysis is
tightly regulated and, in fact, there are widespread examples across eukaryotes of intron retention.
Nonetheless, the regulatory consequences of this phenomenon remain obscure. Guided by strong
preliminary data, we explore both of these outstanding challenges and address the following
questions: (1) How does chromatin influence spliceosome assembly and vice versa, i.e. how does
co-transcriptional spliceosome assembly affect the state of the chromatin? (2) How does intron
retention contribute to gene regulation? (3) How does mis-regulation of intron accumulation lead to
cellular toxicity and disease?

## Key facts

- **NIH application ID:** 10889947
- **Project number:** 5R35GM149290-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** TRACY L JOHNSON
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $393,750
- **Award type:** 5
- **Project period:** 2023-07-18 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889947

## Citation

> US National Institutes of Health, RePORTER application 10889947, Mechanisms of messenger RNA splicing and RNA processing regulation (5R35GM149290-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10889947. Licensed CC0.

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