# Project 6: Regulation and Function of Extended 3' UTR Transcripts in the Nervous System

> **NIH NIH P20** · UNIVERSITY OF NEVADA RENO · 2020 · $319

## Abstract

PROJECT SUMMARY/ABSTRACT 
Regulation and Function of Extended 3´ UTR Transcripts in the Nervous System 
More than 50% of genes in diverse organisms undergo Alternative Cleavage and PolyAdenylation (APA) to 
generate multiple 3´ UTR mRNA isoforms. Thousands of novel extended 3´ UTRs have been recently 
identified to be preferentially expressed in the nervous system of fly, mouse and human. Such a pervasive and 
cell-specific event is likely to have wide-ranging physiologically relevant consequences for nervous system 
development, maintenance and disease. However, to date, few functional roles for extended 3´ UTRs have 
been identified. The long-term objectives are to uncover functions for these extended 3´ UTR isoforms in the 
nervous system, and elucidate the mechanisms of their biogenesis and biological activity. The focus is on a set 
of genes that play established roles in axon guidance. More than ten genes with roles in axon guidance 
express short and extended 3´ UTR isoforms, suggesting that APA is an important regulator for this key 
neurodevelopmental event. Some of these genes have direct relevance to human disease. For instance, 
mutations in calmodulin genes are implicated in multiple cardiac defects in humans. To investigate extended 3´ 
UTR function, CRISPR genome editing is employed to specifically delete these isoforms in Drosophila. This 
approach has been established, and preliminary work has uncovered that impairment of an extended 3´ UTR 
isoform, while leaving the short 3´ UTR isoforms intact, can impair nervous system development. In Aim 1, this 
approach is expanded to cam, the Drosophila calmodulin gene. In Aim 2, the role that chromatin modifications 
have on the biogenesis of extended 3´ UTRs is investigated. This builds upon ongoing work on the mechanism 
through which the ELAV regulates 3´ UTR extension. Overall, this work will establish APA as a crucial 
mechanism governing multiple genes that control axon guidance.

## Key facts

- **NIH application ID:** 9984410
- **Project number:** 5P20GM103650-09
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** Pedro Miura
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $319
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984410

## Citation

> US National Institutes of Health, RePORTER application 9984410, Project 6: Regulation and Function of Extended 3' UTR Transcripts in the Nervous System (5P20GM103650-09). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9984410. Licensed CC0.

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