Tuesday, July 1, 2025 7/1/2025

Gene Expression Modulated by G4, R-loop and DNA Supercoiling

Award Number: R01GM149729
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/21/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2027

Group Awards By:

View Award Description

Gene Expression Modulated by G4, R-loop and DNA Supercoiling - PROJECT SUMMARY G-qudruplex (G4) is a noncanonical secondary structure that can form in both DNA and RNA. Human genome contains over 400,000 potential G4 forming sequences (PQS) and they are highly enriched in upstream of oncogene promoters and regulatory genes, strongly suggesting a switch-like function with programed positioning. PQS is also prevalent in e. coli genome, located in important regulatory regions. Indeed, many studies have demonstrated the role of G4 in up or downregulating genomic processes including replication, transcription and translation. Our recent study demonstrated that in transcription, G4 forming sequence located in the non- template strand leads to a robust formation of R-loop (mRNA annealed to template strand), which in turn, induces G4 structure in the non-template strand. Remarkably, such R-loop/G4 structure drives enhanced transcription by a mechanism that involves successive formation and release of R-loop. We show that when positioned in a plasmid i.e under torsional constraint, such G4/R-loop structure can tune the transcription activity up or down depending on the distance from the transcription start site. Furthermore, 5’UTR-G4 bearing mRNA (RG4) leads to over 10-fold enhanced translation in a cell-free system and in e.coli cells. Upon testing several plausible hypotheses, we propose that the RG4 structure promotes translation by blocking ribosomes from sliding off the mRNA. Building on these exciting new findings, we propose to investigate the impact of G4, R-loop and supercoiling in transcription and translation primarily in T7 RNAP system and in e. coli cells. By combining quantitative biochemical tools and newly developed single molecule platforms suited to measure stepwise progression of transcription in a linear or plasmid DNA, we will examine how different sequence, length and position of G4 forming sequence leads to R-loop formation, mRNA output and protein production. Accomplishing the proposed goals will reveal the structure-function relationship of how G4, R-loop and supercoiling regulates transcription and translation activity.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $318,600 )
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	4	2/19/2025	NON-COMPETING CONTINUATION	$318,600
														Subtotal = $318,600

Issue Date FY: 2024 ( Subtotal = $538,348 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	004	3	8/19/2024	SUPPLEMENT FOR EXPANSION	$157,848
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	002	3	3/4/2024	NON-COMPETING CONTINUATION	$318,600
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	003	3	6/26/2024	NON-COMPETING CONTINUATION	$35,400
2024	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	001	2	12/7/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$354,000
2024	2023	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	1	12/6/2023	NEW	-$327,500
														Subtotal = $538,348

Issue Date FY: 2023 ( Subtotal = $327,500 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	1	3/21/2023	NEW	$327,500
														Subtotal = $327,500

Grand Total All Awards = $1,184,448

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Gene Expression Modulated by G4, R-loop and DNA Supercoiling

Award Number: R01GM149729

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/21/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer