# Biogenesis and Function of Regulatory RNAs

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $526,314

## Abstract

PROJECT SUMMARY
In the past twenty years, thousands of non-coding RNAs (ncRNAs) have been discovered as potential
regulators of gene expression. Within this group, microRNAs (miRNAs) have emerged as essential
mediators of post-transcriptional gene regulation, and defects in specific miRNA pathways have been
linked to numerous human diseases. While a basic understanding of how miRNAs are expressed and
function has been achieved, outstanding questions regarding the regulation of miRNA biogenesis and
target recognition in vivo remain to be solved. Caenorhabditis elegans worms have proven to be an
advantageous model to investigate miRNA biology at the organismal level. The development of
sensitive biochemical methods, unique worm strains, extensive genomic datasets, and robust
computational pipelines has enabled novel insights into miRNA expression and targeting in the context
of a developing animal. Utilizing and further innovating these resources and methods, the proposed
research will contribute to a better understanding of how miRNAs find and regulate targets within a live
animal under ideal as well as stressful conditions. With a confident set of targets bound by the miRNA
complex in vivo, features that underlie the different mechanisms deployed to regulate them will be
deduced. The identification of numerous ncRNAs, including miRNAs and long non-coding RNAs
(lncRNAs), induced by heat shock in C. elegans sets a foundation for discovering new mechanisms for
regulating gene expression in response to this stress. The discovery that the miRNA pathway plays a
key role during heat shock recovery, highlights the importance of this under-explored phase of the heat
shock response. The current research is focused on elucidating how the expression of specific miRNAs
and lncRNAs is regulated by heat shock and, in turn, how these ncRNAs function to protect the
organism during this stress. Over the next five years, these studies have the potential to reveal novel
roles for ncRNAs in response to heat shock and set the stage for investigating the impact of ncRNA
pathways in the organismal response to other stresses, including disease states. The long-term goal
of this research program is to contribute new insights into how ncRNAs control gene expression under
varied conditions in an intact organism. Furthermore, knowledge gained from these studies has the
potential for significant impact on the design and utilization of RNA-based therapeutics for the treatment
of human disease.

## Key facts

- **NIH application ID:** 10620494
- **Project number:** 2R35GM127012-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** AMY E. PASQUINELLI
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $526,314
- **Award type:** 2
- **Project period:** 2018-07-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10620494

## Citation

> US National Institutes of Health, RePORTER application 10620494, Biogenesis and Function of Regulatory RNAs (2R35GM127012-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10620494. Licensed CC0.

---

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