# Regulation of mRNA fate

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2022 · $371,425

## Abstract

Abstract
 The process of alternative splicing (AS) is a powerful mechanism for generating mRNA diversity from
protein coding genes. Alternative mRNA isoforms from the same gene can differ subtly from each other or
have radical alterations in their sequence composition. Remarkably, very little is known about whether or not
this diverse pool of mRNA is converted to protein. One intriguing clue for solving this problem comes from our
recent studies suggesting that the process of alternative splicing influences the translational efficiency of the
resultant mRNA isoforms. In this proposal, we use both biochemical and molecular approaches to untangle the
intricate mechanisms coupling post-transcriptional gene expression. By determining how AS-TC elements reg-
ulate mRNA translation we will be able to refute or support the central hypothesis of this proposal, that alterna-
tively spliced transcripts are packaged into functionally distinct messenger ribonucleoprotein particles
(mRNPs). If sequences associated with differential polyribosome association do not directly control translation
initiation or elongation, then we will consider our alternative hypothesis: that a significant fraction of mRNA iso-
form diversity arises from noisy splicing which are then excluded from polyribosomes by some unknown mRNA
surveillance pathway. Solving this important problem will not only reveal how cis-elements influence transla-
tional yield, but will also define mechanistic links between the processes of alternative splicing and mRNA
translation. In the long-term, our research program will facilitate new opportunities for RNA-based diagnostics
and therapies that will be applicable to a wide array of human diseases.

## Key facts

- **NIH application ID:** 10318148
- **Project number:** 5R35GM130361-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Jeremy Robert Sanford
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $371,425
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318148

## Citation

> US National Institutes of Health, RePORTER application 10318148, Regulation of mRNA fate (5R35GM130361-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10318148. Licensed CC0.

---

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