# Regulation, evolution, and function of promoter-associated non-coding RNAs

> **NIH NIH R35** · UNIVERSITY OF CONNECTICUT STORRS · 2021 · $402,500

## Abstract

PROJECT SUMMARY / ABSTRACT
LEIGHTON CORE, Ph.D. – UNIVERSITY OF CONNECTICUT=
Proper regulation of RNA transcription is essential for dynamic control of cellular responses to environmental
and developmental cues. Dogmatic shifts in the fields of transcription regulation and RNA biology have led us
to appreciate that noncoding RNAs (ncRNAs) can regulate transcription of protein-coding genes by diverse
mechanisms such as recruitment of activators or repressors to gene promoters and enhancers or by affecting
RNA processing. In addition to the role of the RNA, the act of transcription itself can positively or negatively
influence promoter activity when transcription patterns overlap. These observations suggest that regulation of
ncRNA biogenesis adds an intricate layer of control to overall gene expression levels. This proposal aims to 1)
identify the mechanisms that regulate ncRNA production and destruction, 2) determine ncRNA effect on local
protein-coding gene transcription and RNA processing, and 3) investigate the ability of ncRNAs to as
capacitors for evolution of new genes. The major obstacles in understanding the full impact of ncRNAs on
gene transcription is comprehensive identification of non-coding transcripts and methods to functionally classify
them. The work proposed here will develop new experimental and computational methods for comprehensive
identification of transcripts and a classification scheme that will predict function. We will experimentally test our
functional predictions and use the results to inform further revision of our classification system. We will focus
on ncRNAs that overlap with or emanate from protein-coding promoters to determine if they are regulated by
independent signaling pathways and whether their level of production influences expression from the protein-
coding gene. Finally, using an evolutionary model to identify nucleotide changes associated with altered
ncRNA transcript production and processing, we will identify and test mechanisms that are involved in ncRNA
regulation and how they may serve as a platform for gene birth during evolution. These studies will create
functional transcript annotations that will be a primary resource for those studying gene expression in any
context. In addition, our investigation of ncRNA regulation and evolution will serve as foundational work
towards determining how these transcripts affect development, disease, and acquisition of new phenotypes.

## Key facts

- **NIH application ID:** 10248356
- **Project number:** 5R35GM128857-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Leighton James Core
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $402,500
- **Award type:** 5
- **Project period:** 2018-09-13 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248356

## Citation

> US National Institutes of Health, RePORTER application 10248356, Regulation, evolution, and function of promoter-associated non-coding RNAs (5R35GM128857-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10248356. Licensed CC0.

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