# The Control of Gene Expression by Eukaryotic Ribonucleases

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $394,636

## Abstract

Project Summary/Abstract
RNA degradation plays multiple essential functions in the control of gene expression. It
not only regulates global transcript abundance, but also provides quality control
mechanisms to eliminate improperly processed or mis-localized transcripts, or those
containing premature translation termination codons (PTCs). Work in our laboratory
focuses on two major RNA degradation pathways in eukaryotic cells: Nonsense-
Mediated Decay (NMD), which degrades PTC-containing transcripts, and the Exosome,
which processes a variety of non-coding RNAs and also degrades transcripts during
quality-control processes. A combination of genomic approaches and classical genetic
and biochemical analyses has allowed us to identify new roles for these pathways in
gene regulation, including proofreading of splice site selection, regulation of specific
mRNAs and the mechanisms underlying distinct modes of Pol.II termination. We have
also identified the molecular consequences of clinical mutations in exosome subunits
implicated in pontocerebellar hypoplasia (PCH). The work proposed in this application
will broadly expand our understanding of the role of the subunits of the exosome and of
its associated factors on RNA processing and degradation genome-wide. In addition, we
will determine how the activity of the exosome is controlled during stress, and how it
cooperates with other RNA quality control pathways such as those coupled to
translation. Finally we will characterize the mechanisms that promote 3´-end formation
for a novel class of mRNAs, which use a mechanism completely independent from the
classical cleavage and polyadenylation pathway. Overall, the proposed studies will
provide major advances in our understanding of the mechanisms involved in eukaryotic
post-transcriptional regulations and RNA processing.

## Key facts

- **NIH application ID:** 9836858
- **Project number:** 5R35GM130370-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Guillaume F Chanfreau
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $394,636
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836858

## Citation

> US National Institutes of Health, RePORTER application 9836858, The Control of Gene Expression by Eukaryotic Ribonucleases (5R35GM130370-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9836858. Licensed CC0.

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