# Prokaryotic Transcription Termination R37GM041376-R01GM041376 - Competitive Renewal Resubmission 1

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2024 · $535,047

## Abstract

PROJECT SUMMARY
In the bacterium Escherichia coli, ~40% of transcription termination is factor-dependent termination, mediated
by the ATP-dependent RNA translocase Rho, and ~60% of transcription termination is intrinsic termination,
mediated by sequences at which transcription yields an RNA hairpin followed by an RNA U-tract.
In the archaeon Thermococcus kodakarensis, most transcription termination is factor-dependent termination,
mediated by the endoribonuclease and processive exoribonuclease aCPSF1 (archaeal cleavage and
polyadenylation specificity factor 1).
Bacterial and archaeal transcription initiation and transcription elongation and their regulation are well
understood, but bacterial and archaeal transcription termination and its regulation are poorly understood.
Structures of a minimal functional factor-dependent pre-termination complex, a minimal functional intrinsic
pre-termination complex, and a post-termination complex have become available only very recently, and no
structural information whatsoever is available for steps in termination between formation of a pre-termination
complex and formation of a post-termination complex.
We propose to determine structures of intact, complete functional bacterial and archaeal factor-dependent
pre-termination complexes, to determine structures of intact, complete functional bacterial intrinsic
pre-termination complexes, and, most important, to obtain structural and functional information for
intermediates in termination between formation of a pre-termination complex and formation of a
post-termination complex. Our results will test directly the "RNAP hypertranslocation," "RNA extraction," and
"allosteric" hypotheses for termination, will distinguish directly between "external force" and "invasion" models
for termination, and will define, comprehensively, the protein-DNA, protein-RNA, and protein-protein
interactions in factor-dependent termination, intrinsic termination, and Q-dependent antitermination.
The proposed work will use cryo-EM, single-molecule picometer-resolution nanopore tweezers (SPRNT), and
deep sequencing to address three Specific Aims:
Aim 1: Define the structural and mechanistic basis of factor-dependent transcription termination
Aim 2: Define the structural and mechanistic basis of intrinsic transcription termination
Aim 3: Define the structural and mechanistic basis of Q-dependent transcription antitermination
The proposed work will contribute directly to understanding bacterial and archaeal transcription and
transcriptional regulation. Because bacterial RNAP and, especially, archaeal RNAP show sequence, structural,
and mechanistic similarities to eukaryotic RNAP, the results also will contribute to understanding eukaryotic
transcription and transcriptional regulation.

## Key facts

- **NIH application ID:** 10898876
- **Project number:** 5R01GM041376-36
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** RICHARD H. EBRIGHT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $535,047
- **Award type:** 5
- **Project period:** 1988-12-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898876

## Citation

> US National Institutes of Health, RePORTER application 10898876, Prokaryotic Transcription Termination R37GM041376-R01GM041376 - Competitive Renewal Resubmission 1 (5R01GM041376-36). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10898876. Licensed CC0.

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