# Mechanisms of the spliceosome protein SF3B1 and inhibitors

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2020 · $39,664

## Abstract

PROJECT SUMMARY
The long-term goal of our research is to build a mechanistic model of spliceosome function. The
spliceosome catalyzes pre-mRNA splicing, which is a crucial step in eukaryotic gene expression, and
abnormal splicing underlies many human diseases, including cancers. Understanding this critical
cellular machine in normal, healthy situations is the necessary first step to determining how aberrant
changes in spliceosome activity is linked to cancer. The spliceosome consists of over 100 proteins,
and we lack mechanistic information for the vast majority of them. One of the core spliceosome
proteins is SF3B1, which is frequently mutated in several different types of cancer. SF3B1 is also the
target of natural anti-tumor products. Our objectives are to determine the role of the spliceosome core
protein SF3B1 in the spliceosome assembly process and to determine the structure activity
relationships of SF3B1 inhibitors. We will achieve these goals using an in vitro splicing system to
characterize the effect of synthetic inhibitor analogs. Our research on SF3B1 is significant because
deciphering the function of a core spliceosome protein will fill a large gap in our mechanistic
understanding of the splicing process. Furthermore, understanding the role of SF3B1 promises to
impact active research efforts to uncover the dependence of cancer cells on splicing, and to inform the
development of new chemotherapeutics based on splicing modulation.

## Key facts

- **NIH application ID:** 10003678
- **Project number:** 3R01GM122279-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Melissa S Jurica
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,664
- **Award type:** 3
- **Project period:** 2020-01-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003678

## Citation

> US National Institutes of Health, RePORTER application 10003678, Mechanisms of the spliceosome protein SF3B1 and inhibitors (3R01GM122279-03S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10003678. Licensed CC0.

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