# Exploring the connections between translation and mRNA decay

> **NIH NIH R35** · UNIVERSITY OF COLORADO DENVER · 2021 · $22,156

## Abstract

SUMMARY
It has been recognized for decades that post-transcriptional regulation is as important as
transcription for controlling gene expression, but much of post-transcriptional regulation
is a black box. Alterations in post-transcriptional regulation can lead to disease, such as
neurodegeneration, developmental defects, and cancer. One area of post-transcriptional
regulation that remains in its infancy of understanding is how mRNA stability is affected
by other events in the mRNA life cycle, such as translation. An overarching theme has
been that repression of translation initiation precedes and causes mRNA decay, but
there are many contradictory examples to this generalization. Here, we focus on two
systems outside this generalization. First, my lab has made a significant advance in
delineating translational repression in the absence of mRNA decay during early
Drosophila embryogenesis through our discovery that the post-transcriptional repressor
ME31B has different regulatory impacts before and after the MZT. ME31B represses
translation before the MTZT, but stimulates mRNA decay after. We have found that
ME31B represses translation through an eIF4E-binding protein called Cup, which is
degraded during the MZT. Thus, a critical, unresolved issue is why ME31B fails to
stimulate mRNA decay before the MZT. Work from my lab and others points to a
potential role for Cup in blocking mRNA decay. We will address this issue by answering
two questions. 1) What is the role of Cup in embryogenesis?; 2) How is mRNA
decapping generally controlled during embryogenesis? Our second area of research is
understanding how translation elongation affects mRNA decay. Work in model
prokaryotic and eukaryotic systems has demonstrated that codon optimality affects
mRNA stability. By developing a suite of new transcriptome-wide experimental and
computational tools, my lab has found that translation elongation also alters mRNA
stability in humans and that these changes are mediated partially through codon usage.
Here, we will answer two related questions: 3) How does translation elongation affect
mRNA stability in humans?; 4) What is the role of codon optimality in controlling gene
expression? To do so, we will combine genetic, genome-wide, and classical molecular
biology approaches. The outcomes of our research will be an improved understanding of
post-transcriptional regulation, and our insights may inform our view of how gene
misregulation underlies human disease.

## Key facts

- **NIH application ID:** 10468440
- **Project number:** 3R35GM128680-04S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Olivia Selfridge Rissland
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $22,156
- **Award type:** 3
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468440

## Citation

> US National Institutes of Health, RePORTER application 10468440, Exploring the connections between translation and mRNA decay (3R35GM128680-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10468440. Licensed CC0.

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