# Regulation of microRNA Strand Selection in Caenorhabditis elegans

> **NIH NIH F32** · KANSAS STATE UNIVERSITY · 2022 · $67,582

## Abstract

Project Summary/Abstract
Precise control of gene expression programs is critical to maintain cellular homeostasis and ensure normal
animal development. Improper gene expression is associated with numerous human pathologies, highlighting
the importance of regulated gene expression. microRNAs (miRNAs) are key regulators of eukaryotic gene
expression. Although more than half of all human mRNAs are predicted targets of miRNAs, our understanding
of how miRNA-meditated gene repression is achieved remains incomplete. A critical step of miRNA-dependent
gene regulation is the processing of stem-loop miRNA precursors into double-stranded miRNA duplexes. Each
miRNA duplex comprises two strands destined for different fates: one strand is loaded into an Argonaute effector
protein to form the miRNA-induced silencing complex (miRISC), while the other strand is degraded. As either
miRNA strand can be functional, the decision of which miRNA strand is loaded into Argonaute effectively
determines the target repertoire of miRISC. Improper miRNA strand choice can have severe consequences, as
alternative miRNA strand selection has been observed in numerous human diseases including atrial fibrillation,
multiple sclerosis, and several cancers. The objective of this proposal is to investigate the regulatory
mechanisms of miRNA strand selection in vivo using the genetically amenable C. elegans model system. I will
establish the hierarchy of miRNA duplex intrinsic and extrinsic features towards the regulation of miRNA strand
selection. My central hypothesis is that external regulatory factors can override nucleotide sequence cues to
regulate miRNA strand selection in a ‘switch-like’ fashion. Overall, completion of this proposal will significantly
expand our understanding of how miRNA strand selection is regulated in the complex context of a developing
organism. These findings should provide fundamental insights necessary to understand how miRNA strand
selection becomes disrupted in human disease.

## Key facts

- **NIH application ID:** 10537071
- **Project number:** 1F32GM148040-01
- **Recipient organization:** KANSAS STATE UNIVERSITY
- **Principal Investigator:** Jeffrey Christopher Medley
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 1
- **Project period:** 2022-08-08 → 2024-08-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537071

## Citation

> US National Institutes of Health, RePORTER application 10537071, Regulation of microRNA Strand Selection in Caenorhabditis elegans (1F32GM148040-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10537071. Licensed CC0.

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