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Prokaryotic Transcription Termination R37GM041376-R01GM041376 - Competitive Renewal Resubmission 1

Award Number: R01GM041376
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: 12/01/1988
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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


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 = $535,760 )
2025	2025	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	37	6/12/2025	NON-COMPETING CONTINUATION	$535,760
														Subtotal = $535,760

Issue Date FY: 2024 ( Subtotal = $758,912 )
2024	2024	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	002	36	8/21/2024	SUPPLEMENT FOR EXPANSION	$223,865
2024	2024	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	001	36	6/13/2024	NON-COMPETING CONTINUATION	$535,047
2024	2023	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	35	3/20/2024	COMPETING CONTINUATION	$0
														Subtotal = $758,912

Issue Date FY: 2023 ( Subtotal = $534,373 )
2023	2023	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	35	8/3/2023	COMPETING CONTINUATION	$534,373
														Subtotal = $534,373

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2012	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	24	1/23/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $374,706 )
2012	2012	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	001	24	4/18/2012	NON-COMPETING CONTINUATION	$30,817
2012	2012	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	24	11/25/2011	NON-COMPETING CONTINUATION	$343,889
														Subtotal = $374,706

Issue Date FY: 2011 ( Subtotal = $374,706 )
2011	2011	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	23	12/1/2010	NON-COMPETING CONTINUATION	$350,861
2011	2011	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	001	23	9/2/2011	NON-COMPETING CONTINUATION	$23,845
														Subtotal = $374,706

Issue Date FY: 2010 ( Subtotal = $378,588 )
2010	2010	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	001	22	3/17/2010	NON-COMPETING CONTINUATION	$34,417
2010	2010	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	22	11/27/2009	NON-COMPETING CONTINUATION	$344,171
														Subtotal = $378,588

Issue Date FY: 2009 ( Subtotal = $419,738 )
2009	2009	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Trans-NIH Recovery Act Research Support	001	21	9/29/2009	SUPPLEMENT FOR EXPANSION	$48,358
2009	2009	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	21	11/25/2008	COMPETING CONTINUATION	$371,380
														Subtotal = $419,738

Issue Date FY: 2008 ( Subtotal = $302,720 )
2008	2008	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	20	11/29/2007	NON-COMPETING CONTINUATION	$302,720
														Subtotal = $302,720

Issue Date FY: 2007 ( Subtotal = $302,118 )
2007	2007	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Biomedical Research and Research Training	000	19	11/30/2006	NON-COMPETING CONTINUATION	$302,118
														Subtotal = $302,118

Issue Date FY: 2006 ( Subtotal = $301,674 )
2006	2006	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 DAVIDSON ROAD	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Biomedical Research and Research Training	000	18	11/28/2005	NON-COMPETING CONTINUATION	$301,674
														Subtotal = $301,674

Issue Date FY: 2005 ( Subtotal = $301,621 )
2005	2005	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 DAVIDSON ROAD	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Biomedical Research and Research Training	000	17	12/30/2004	COMPETING CONTINUATION	$301,621
														Subtotal = $301,621

Issue Date FY: 2004 ( Subtotal = $263,689 )
2004	2004	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 DAVIDSON ROAD	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Biomedical Research and Research Training	000	16	11/26/2003	NON-COMPETING CONTINUATION	$263,689
														Subtotal = $263,689

Issue Date FY: 2003 ( Subtotal = $263,689 )
2003	2003	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 DAVIDSON ROAD	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Cell Biology and Biophysics Research	000	15		NON-COMPETING CONTINUATION	$263,689
														Subtotal = $263,689

Issue Date FY: 2002 ( Subtotal = $263,689 )
2002	2002	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 DAVIDSON ROAD	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Cell Biology and Biophysics Research	000	14	11/28/2001	NON-COMPETING CONTINUATION	$263,689
														Subtotal = $263,689

Issue Date FY: 2001 ( Subtotal = $263,689 )
2001	2001	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 DAVIDSON ROAD	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Cell Biology and Biophysics Research	000	13	2/5/2001	COMPETING CONTINUATION	$263,689
														Subtotal = $263,689

Issue Date FY: 2000 ( Subtotal = $274,225 )
2000	2000	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Cell Biology and Biophysics Research	000	12	11/26/1999	NON-COMPETING CONTINUATION	$274,225
														Subtotal = $274,225

Issue Date FY: 1999 ( Subtotal = $266,409 )
1999	1999	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Cell Biology and Biophysics Research	000	11	11/18/1998	NON-COMPETING CONTINUATION	$266,409
														Subtotal = $266,409

Issue Date FY: 1998 ( Subtotal = $257,648 )
1998	1998	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Cell Biology and Biophysics Research	000	10	11/21/1997	NON-COMPETING CONTINUATION	$257,648
														Subtotal = $257,648

Grand Total All Awards = $6,437,954

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Prokaryotic Transcription Termination R37GM041376-R01GM041376 - Competitive Renewal Resubmission 1

Award Number: R01GM041376

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: 12/01/1988

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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