# Defining Adaptors for mRNA Degradation in Bacteria

> **NIH NIH F32** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $68,562

## Abstract

PROJECT SUMMARY/ABSTRACT
Transcription and RNA turnover shape the pool of transcripts in the cell. Regulation of RNA degradation,
however, remains elusive when compared to the enumerable mechanisms of transcriptional control. In
bacteria, mRNA decay is thought to be initiated by a few endoribonucleases that have promiscuous activities,
yet mRNA half-lives vary greatly. Here I propose to globally define the set of adaptors for endoribonucleases
that instruct mRNA decay, akin to transcription factors modulating the activity of RNA polymerase.
Only a few adaptors of degradation have been discovered in bacteria, and they were all found serendipitously.
To provide a far more comprehensive view, I will develop several general methodologies that will be
translatable to other organisms. My first approach will identify classes of RNAs potentially targeted by the
same adaptor, using their dependence on nuclease levels as a classifier. Demonstration of this top-down
method utilizes the central endonuclease RNase Y from the gram-positive bacterium Bacillus subtilis.
Completion of the first part of this aim will be the first high-resolution study of RNA degradation in B. subtilis
and demonstrates a general strategy to define the direct targets of promiscuous central endonucleases.
Secondly, to complement the systems-wide approach, I have designed both genetic and biochemical
approaches to identify the molecular constituents of adaptors of degradation. Discoveries of novel adaptors for
mRNA decay will expand our understanding of gene regulation and provide transformative tools for molecular
biology. Together, this set of top-down and bottom-up approaches will transform our understanding of
endonuclease specificity in bacteria and provide a general strategy for studying the post-transcriptional control
of gene expression.
The fellowship training plan leverages complementary expertise and experiences of two mentors, Dr. Gene-
Wei Li and Dr. Alan Grossman. Technical training within the research strategy consists of (1) quantitative
modeling and next-generation sequencing techniques from my sponsor Dr. Li and (2) methodologies in forward
genetics assays and nucleic acid biochemistry from my co-sponsor Dr. Grossman. Dr. Li is a trained physicist
and has a record of developing cutting-edge approaches to address his unique perspective on gene regulation.
Dr. Grossman is a renowned bacterial geneticist and has thirty years of mentorship experience as a professor
with many postdoctoral trainees obtaining independent research positions. The combined environment
fostered by these two individuals at the Massachusetts Institute of Technology serves to address the aims of
the research proposed and to aid in my development as an independent researcher.

## Key facts

- **NIH application ID:** 10132728
- **Project number:** 5F32GM134568-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Matthew Tien
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 5
- **Project period:** 2020-04-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132728

## Citation

> US National Institutes of Health, RePORTER application 10132728, Defining Adaptors for mRNA Degradation in Bacteria (5F32GM134568-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10132728. Licensed CC0.

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