# Determining the factors that control dose-dependent splicing regulation by a master regulator

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $414,445

## Abstract

Many trans and cis acting factors that control alternative splicing have
been identified. The explosion of next-generation sequencing approaches have
identified thousands of regulated splicing events (RNA-seq), and binding sites of
many proteins which regulate alternative splicing have been identified via
CLIPseq. An important question remaining for the field is: What are the rules
governing the behavior of alternative splicing decisions? For example, what are
the RNA elements (sequence and structure) that determine if alternatively
regulated exons will respond at low concentrations or at high concentrations to a
splicing factor, and will the splicing responses exhibit cooperative behavior or
not? Addressing these questions is important for providing a framework for
understanding how changes in splicing factor concentration can lead to disease.
To address these questions, we have created cellular models that allow us to
precisely titrate the level of an alternative splicing regulator, the Muscleblind-like
1 (MBNL1) protein. MBNL1 has been shown to regulate thousands of alternative
splicing events and is important for the development of skeletal muscle, heart
and the central nervous system. This regulation is highlighted by the primary role
that MBNL proteins play in the disease myotonic dystrophy (DM), in which
MBNL1 and its paralogs (MBNL2 and MBNL3) are sequestered by expanded
CUG or CCUG repeat RNAs, resulting in aberrant RNA processing. The mis-
splicing of MBNL targets has been shown to be responsible for causing some of
the symptoms associated with DM, including the hallmark symptom myotonia.
 .

## Key facts

- **NIH application ID:** 9902459
- **Project number:** 5R01GM121862-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Andrew Berglund
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $414,445
- **Award type:** 5
- **Project period:** 2017-08-04 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902459

## Citation

> US National Institutes of Health, RePORTER application 9902459, Determining the factors that control dose-dependent splicing regulation by a master regulator (5R01GM121862-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9902459. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*