# Biogenesis and Function of Regulatory RNAs

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $379,611

## Abstract

PROJECT SUMMARY
Over the past decade, 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 remain to be solved. In particular, the miRNA pathway has been shown to play an
important role in diverse stress responses, but the mechanisms that control miRNA expression and
activity under non-ideal conditions are poorly understood. 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 and robust computational
pipelines has enabled novel insights into miRNA expression and targeting in the context of a
developing animal. These approaches are now being utilized to understand how miRNAs contribute
to the organismal response to heat stress. Additionally, dozens of novel long non-coding RNAs
(lncRNAs) were found to be induced by heat shock and, already, one of them has been shown to
promote survival during this stress. Thus, multiple ncRNA pathways potentially contribute to the
changes in gene expression needed to survive this stress condition. The proposed 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 5 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. Work aimed at understanding how the 3' poly(A) tail on
messenger RNAs (mRNAs) contributes to binding and regulation by the miRNA complex led to the
surprising discovery that short poly(A) tails are commonly associated with highly expressed genes in
somatic cells. Thus, a new research direction addresses previously unrecognized complexities in
poly(A) tail length control and its relationship to the regulation of gene expression. The long-term goal
of this research program is to contribute new insights into how ncRNAs and regulatory elements in
mRNAs, such as poly(A) tails, control organismal gene expression under varied conditions.
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:** 10200086
- **Project number:** 5R35GM127012-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** AMY E. PASQUINELLI
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $379,611
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200086

## Citation

> US National Institutes of Health, RePORTER application 10200086, Biogenesis and Function of Regulatory RNAs (5R35GM127012-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10200086. Licensed CC0.

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