# Trans-translation-mediated regulation of gene expression by distal REP sequences in E. coli K-12

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $307,000

## Abstract

PROJECT SUMMARY
A novel function for REP family repetitive DNA elements encoded distal and proximal
(<16 bp) to protein-coding regions in the E. coli K-12 genome has been recently
discovered. These elements signal a partial, transient, and reversible translational
stalling mediated through trans-translation resulting in a three-fold modulation of protein
and mRNA levels. This work extended the cellular roles for the essential and universal
trans-translation process to include gene regulation. This research proposal aims to
broadly extend and confirm the initial report, potentially impacting many different areas
of bacterial physiology due to (1) a large number and functional diversity of potentially
regulated genes, (2) the experimental REP element legacy and a wide distribution of
REP elements among both medically threatening and biome healing Enterobaceae, and
(3) the likelihood that the signaling elements are not restricted only to REP-encoded
RNA stem-loops. The complementary goals of this proposal are (1) to elucidate the
biochemical pathways and signaling mechanisms involved experimentally in E. coli K-12
case studies, and (2) to apply bioinformatics to identify, functionally assess, and cluster
genes that all have REPS and other RNA structures <16 bp after stop codons in
common. Specific Aim 1 will determine the sequence requirements of mRNA stem-loops
for the induction of trans-translation. Specific Aim 2 will examine the physiological
significance and roles of REP hairpins, and the examination of physiological inducers,
including the known UV induction in more detail. Specific Aim 3 will explore the
mechanism of initiation of trans-translation by REPs. We will examine the roles of small
mRNA interferases and rare stop codons in REP regulation. Specific Aim 4 will
determine the distribution of predicted REP-arrested genes in the enteric bacteria and
look for functional commonalities, especially their involvement in stress responses.

## Key facts

- **NIH application ID:** 9837449
- **Project number:** 5R01GM118852-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** MURRAY P DEUTSCHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $307,000
- **Award type:** 5
- **Project period:** 2017-02-17 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9837449

## Citation

> US National Institutes of Health, RePORTER application 9837449, Trans-translation-mediated regulation of gene expression by distal REP sequences in E. coli K-12 (5R01GM118852-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9837449. Licensed CC0.

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