# Regulation of Messenger RNA Turnover in Mammalian Cells

> **NIH NIH R35** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $457,480

## Abstract

Project Description
 Research in my laboratory focuses on elucidating the principles and regulatory mechanisms that
govern messenger RNA turnover in mammalian cells. mRNA turnover plays an essential role in regulating
gene expression via control of mRNA stability and quality, both globally and at the level of individual
mRNAs. In mammalian cells, all major modes of mRNA decay are triggered by deadenylation (i.e., the
removal of the poly(A) tails from the 3' end of mRNAs), a rate-limiting process involving two consecutive
kinetic phases. Although previous studies provided a clear picture of the mechanistic steps and
participating factors of mRNA decay pathways, relatively little is known about the impact of deadenylation
and its modulation on mRNA turnover at the transcriptome level. Particularly lacking is an understanding of
how coordinated changes in stability for whole groups of mRNAs contribute to programming or
reprogramming of the transcriptome when mammalian cells respond to intra- or extra-cellular stimuli. In the
cytoplasm, mRNAs fulfill their functions in the form of mRNA-protein complexes (mRNPs). mRNPs are
highly dynamic entities, being continuously remodeled by rapid exchanges of their protein constituents,
dictating individual mRNAs' fates at each step of their lifespan. Any inappropriate remodeling of an mRNP
complex has the potential to disrupt its proper engagement in downstream events. Currently, one exciting
and underexplored area of research in RNA biology is the remodeling of mRNPs at individual, group, and
global levels during the process of mRNA deadenylation and decay.
 Our present proposal focuses on three seemingly disparate aspects of mammalian RNA biology that
are linked by their potential to shape the mammalian transcriptome through modulating global mRNA
turnover and mRNP remodeling. These are: 1) Alternative 3' end processing and polyadenylation (APA),
which generates mRNA isoforms with distinct 3' untranslated regions; 2) mRNA N6-methyladenosine (m6A)
modification, which creates mRNA isoforms with different metabolic fate; and 3) Phosphorylation of
ancillary deadenylation factors, which alters mRNA deadenylation and decay. In the past few years, we
have made several key findings regarding these three areas that have helped lay the groundwork for the
proposed studies in this application. We have also adapted and further developed key analytical
approaches to elucidating the impacts of the targeted processes on mRNA turnover across the
transcriptome and the mechanisms by which deadenylation impacts mRNA stability through mRNP
remodeling. Successful completion of the proposed studies will offer a new framework for elucidating the
signal-dependent regulation of mRNA stability and mRNP remodeling at the transcriptome level, and the
results will significantly expand understanding of the fundamental principles governing eukaryotic mRNA
turnover.

## Key facts

- **NIH application ID:** 9895834
- **Project number:** 5R35GM127109-03
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Ann-Bin Shyu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $457,480
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895834

## Citation

> US National Institutes of Health, RePORTER application 9895834, Regulation of Messenger RNA Turnover in Mammalian Cells (5R35GM127109-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9895834. Licensed CC0.

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