# Regulation of mRNA Fate

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2024 · $410,485

## Abstract

Project Summary
This renewal application focuses on studying the roles of messenger RNA binding proteins
(mRBPs) in the regulation of alternative splicing and mRNA translation. Our approach uses a
combination of genomics, molecular biology and biochemistry to gain fundamental insights to
mRBP function and targets in human cells. During the previous funding period we discovered
functional RNA elements that control pre-mRNA splicing and mRNA translation. The goal of the
next funding period is to determine how these sequences regulate gene expression. Another
goal of this project is to determine how the process of alternative splicing impacts protein
synthesis. It is well established that alternative splicing expands the coding potential of protein
coding genes, but we and others have also discovered that mRNA isoforms can exhibit different
patterns of translational control and mRNA stability. We will elucidate the mechanisms through
which alternative splicing influences translation by discovering isoform-specific cis-acting RNA
elements that influence polyribosome association. To accomplish this goal, we will use
composite cell lines that contain a full complement of human and chimpanzee chromosomes.
These novel models will enable the discovery of single nucleotide changes that cause allele-
specific gene expression within the identical trans-regulatory environment. We can then
determine the mechanisms of action for these regulatory elements using biochemical and
molecular approaches, such as RNA affinity chromatography and mRNA reporter assays.
Together, this project will significantly advance the understanding ofr how mRBPs function in
post-transcriptional control of gene expression in human cells and provide key information for
novel strategies to treat inherited diseases.

## Key facts

- **NIH application ID:** 10842838
- **Project number:** 2R35GM130361-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Jeremy Robert Sanford
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $410,485
- **Award type:** 2
- **Project period:** 2019-01-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842838

## Citation

> US National Institutes of Health, RePORTER application 10842838, Regulation of mRNA Fate (2R35GM130361-06). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10842838. Licensed CC0.

---

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