# Understanding the interconnection between mRNA turnover and mRNA translation

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $368,438

## Abstract

Abstract
Messenger RNA (mRNA) decay is a critical step in the regulation of gene expression. mRNA
decay in eukaryotes proceeds by removal of the 3' poly(A) tail (deadenylation) followed by
removal of the 5' cap (decapping) then destruction of mRNA by 5' - 3' exonuclease digestion.
This process of decay is intimately connected to mRNA translation, and a major goal of the field
is to understand how translation interacts with decay to set decay rates. Our lab has made the
important discovery that codon optimality is a critical determinant of decay rates transcriptome-
wide. Further, we have identified the DEAD-box protein DHH1 as the sensor that detects slowed
translation elongation associated with non-optimal codons and directs these messages to
decapping and degradation. In light of this novel function for DHH1, this proposal seeks to
understand the mechanism by which DHH1 senses slowed translation elongation and transmits
this information to the decapping complex. The first aim is designed to understand how DHH1
interacts with the ribosome to sense slowed elongation. The second aim focuses on how DHH1
transmits a slowed elongation signal to the decapping complex. The third aim is to determine
how deadenylation sensitizes mRNA to DHH1. Together, these aims will inform how DHH1
functions, thus providing insight into a wide range of gene expression events.

## Key facts

- **NIH application ID:** 10177112
- **Project number:** 7R01GM125086-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jeffery Coller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,438
- **Award type:** 7
- **Project period:** 2017-08-10 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177112

## Citation

> US National Institutes of Health, RePORTER application 10177112, Understanding the interconnection between mRNA turnover and mRNA translation (7R01GM125086-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10177112. Licensed CC0.

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