# Genetics and Genomics of Alternative Polyadenylation and miRNA Regulation in C. e - Renewal - 1

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2022 · $316,076

## Abstract

Abstract
3’ Untranslated Regions (3’UTR) are mRNA ends located between the STOP codon and the polyA tail. They
contain numerous regulatory elements that are poorly characterized, making them a core target for post-
transcriptional regulation of gene expression by miRNAs and RNA binding proteins. MiRNAs are small
regulatory RNAs that bind 3’UTRs and repress mRNA translation. Our group and others have shown that
alternative polyadenylation (APA), an elusive process observed in metazoans that gives rise to genes with
various 3’UTR isoforms, is widespread. While APA is frequently present in normal states and in virtually all
diseases, its biological role in cells and tissues is a mystery. Genes with longer 3’UTRs have more potential
regulatory sites, thus APA may allow genes to alter their 3’UTR length and escape the repression by miRNAs
and RNA binding proteins. Since APA is abundant this could explain why there is not a direct correlation
between cellular transcriptomes and proteomes. Understanding the global mechanics of 3’end formation, APA
function, and miRNA targeting would advance research on post-transcriptional modifications. Metazoans
possess hundreds of miRNAs and thousands of 3’UTR isoforms, most of which are expressed and function in
different tissues and developmental contexts. We know little about how these networks operate and
communicate with each other, despite their critical role in controlling gene expression. We need to gain new
data and insights, and develop a high-resolution miRNAs/3’UTRs Interactome by acquiring and fusing tissue-
specific miRNA localization data, miRNA target data, and 3’UTRs isoform data. Our Interactome will provide
the global basis of post-transcriptional gene regulation function in vivo, elucidating its role in both normal and
disease states in metazoans. In our first R01 grant we studied tissue-specific APA events and miRNA networks
in the nematode C. elegans, to define and probe the worm miRNAs/3’UTRs Interactome. We identified 3’UTR
isoforms in eight C. elegans somatic tissues, acquired miRNA expression data for the three largest and
disease-relevant C. elegans worm tissues, developed and implemented unbiased methods to map miRNA
targets in high throughput, and initiated mechanistic studies of APA selection in genes identified in our studies.
For this new submission we will, (1) complete the worm 3’UTRome by including new tissue-specific 3’UTR
isoforms, (2) identify tissue-specific miRNA populations in eight worm somatic tissues and, (3) perform
mechanistic studies to determine tissue-specific PAS choice in the context of APA. Our curated 3’UTRome will
be the first database to provide a complete metazoan 3’UTRome mapped at a single base resolution.
Investigating three global hypotheses of PAS choice can uncover global post-transcriptional gene regulatory
mechanisms implicated in tissue development and disease, and therefore of high impact. We believe that the
impact of these new studies is high since w...

## Key facts

- **NIH application ID:** 10454976
- **Project number:** 5R01GM118796-07
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Marco Mangone
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $316,076
- **Award type:** 5
- **Project period:** 2016-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454976

## Citation

> US National Institutes of Health, RePORTER application 10454976, Genetics and Genomics of Alternative Polyadenylation and miRNA Regulation in C. e - Renewal - 1 (5R01GM118796-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10454976. Licensed CC0.

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