# Regulation of gene expression and genome organization by small RNAs

> **NIH NIH R35** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $412,500

## Abstract

Project Summary: Small RNAs regulate gene expression in a wide range of organisms from yeasts to
humans and the fundamental mechanisms governing RNA silencing are conserved across most eukaryotes.
The term “small RNA” encompasses a diverse set of small regulatory RNAs, ranging from ~18-30 nucleotides
in length, all bound by members of the Argonaute protein family. The first small RNAs identified were
microRNAs, discovered in C. elegans as regulators of development timing (Ambros and Ruvkun labs). Several
years later, the phenomenon of RNA interference (RNAi), gene silencing induced by the introduction of double
stranded RNA, was also discovered in C. elegans (Fire and Mello labs). Much work since then has uncovered
the roles of a diverse set of proteins that regulate genes by way of small RNAs at the level of transcription,
translation, and mRNA stability. By regulating both endogenous and foreign RNAs, small RNAs play a critical
role in development, genome stability, and viral defense.
 The goal of this research program is to investigate the mechanisms by which RNA silencing pathways
modulate gene expression and maintain genome integrity. Like Ambros, Ruvkun, Fire, and Mello, we will use
the nematode, C. elegans, as a model system to study RNA silencing because worms combine the best of
genetic, cytological, molecular, and biochemical tools. There are many fundamental unanswered questions in
our understanding of RNA silencing that we plan to address in this proposal.
 We and others have determined the localization for many factors in the RNA silencing pathway but there
has been little to no cytological exploration the RNA and DNA components. Furthermore, the mechanism by
which targeted transcripts are recognized and routed into the RNA silencing pathways is unknown. Our first
goal is to localize the mRNAs targeted by RNA silencing and to determine the protein requirements for their
physical movement from transcription in the nucleus to turnover in the cytoplasmic RNA silencing
compartment, the Mutator foci. We will further examine whether RNA silencing affects the subnuclear
positioning of the targeted gene loci, to promote mRNA localization and RNA silencing.
 Despite much work in the field, there are proteins attributed to small RNA pathway for which the
mechanism of action is unknown. We also believe there are components of the pathway that have yet to be
identified. Our second goal is to use a combination of molecular biology and cytology to examine
uncharacterized components of the pathway in the processes of recruitment and retention of RNA in the
Mutator foci and in modification of mRNA targets. Our third goal is to identify and characterize new
components of the RNA silencing complex using proteomics. This research will shed light on conserved
pathways that regulate gene expression and are critical for development, antiviral immunity, and genome
organization.

## Key facts

- **NIH application ID:** 9977251
- **Project number:** 5R35GM119656-05
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Carolyn Marie Phillips
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977251

## Citation

> US National Institutes of Health, RePORTER application 9977251, Regulation of gene expression and genome organization by small RNAs (5R35GM119656-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9977251. Licensed CC0.

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