Wednesday, February 5, 2025 2/5/2025

Histone mRNA Regulation in Development

Award Number: R01GM058921
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT Proper regulation of histone biosynthesis during the cell cycle is critical for coordinating chromatin assembly and DNA replication. Overproduction or underproduction of histone protein results in replication stress and genome instability that contributes to the development of cancer. In this proposal, we undertake a comprehensive analysis of replication-dependent (RD) histone mRNA biosynthesis and how this process is regulated during the cell cycle in the context of animal development. RD-histone mRNAs are the only eukaryotic mRNAs in animal cells that lack a polyA tail, ending instead in a conserved stem loop structure. In contrast, mRNAs for histone variants such as H3.3 and H2A.Z are encoded by polyadenylated mRNAs that are not cell cycle regulated. Generation of the unique RD-histone mRNA 3’ end results from the activity of an evolutionary conserved set of pre-RNA processing factors. The genes encoding all five RD-histone proteins are clustered in metazoan genomes, and transcription and pre- mRNA processing factors required for histone mRNA biosynthesis are organized into a nuclear body (the histone locus body or HLB) that assembles at these gene clusters. We will determine the requirements for the coordinate synthesis of the RD-histone mRNAs using both biochemical and genetic approaches in Drosophila, with a particular focus on the role that the HLB plays in histone transcription and pre-mRNA processing. Histone gene clusters provide a system in which one can readily study the expression of a tightly regulated set of genes at all levels of mRNA biosynthesis, from the organization of genes within the nucleus through activation of transcription, pre-mRNA processing and transcription termination. Our Drosophila experimental paradigm permits the in vivo interrogation of these fundamental processes in gene expression in ways that are unavailable in other experimental systems.


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 = $260,243 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	24	12/5/2024	SUPPLEMENT FOR EXPANSION	$260,243
														Subtotal = $260,243

Issue Date FY: 2024 ( Subtotal = $645,493 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	24	11/15/2023	NON-COMPETING CONTINUATION	$580,945
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	24	6/20/2024	NON-COMPETING CONTINUATION	$64,548
														Subtotal = $645,493

Issue Date FY: 2023 ( Subtotal = $645,502 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	23	11/8/2022	NON-COMPETING CONTINUATION	$580,951
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	23	2/14/2023	NON-COMPETING CONTINUATION	$64,551
														Subtotal = $645,502

Issue Date FY: 2022 ( Subtotal = $645,564 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	22	11/15/2021	NON-COMPETING CONTINUATION	$581,007
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	22	6/9/2022	NON-COMPETING CONTINUATION	$64,557
														Subtotal = $645,564

Issue Date FY: 2021 ( Subtotal = $645,564 )
2021	2021	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	002	21	7/11/2021	COMPETING CONTINUATION	$1,718
2021	2021	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	21	12/9/2020	COMPETING CONTINUATION	$645,564
2021	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	20	7/11/2021	NON-COMPETING CONTINUATION	-$1,718
														Subtotal = $645,564

Issue Date FY: 2020 ( Subtotal = $610,981 )
2020	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	20	2/27/2020	NON-COMPETING CONTINUATION	$61,099
2020	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	20	11/25/2019	NON-COMPETING CONTINUATION	$549,882
														Subtotal = $610,981

Issue Date FY: 2019 ( Subtotal = $610,981 )
2019	2019	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	19	8/6/2019	NON-COMPETING CONTINUATION	$0
2019	2019	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	19	11/27/2018	NON-COMPETING CONTINUATION	$610,981
														Subtotal = $610,981

Issue Date FY: 2018 ( Subtotal = $610,981 )
2018	2018	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	18	11/14/2017	NON-COMPETING CONTINUATION	$549,882
2018	2018	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	18	5/24/2018	NON-COMPETING CONTINUATION	$61,099
														Subtotal = $610,981

Issue Date FY: 2017 ( Subtotal = $747,776 )
2017	2017	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	004	17	8/30/2017	SUPPLEMENT FOR EXPANSION	$136,795
2017	2017	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	003	17	5/12/2017	COMPETING CONTINUATION	$1,716
2017	2017	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	17	12/16/2016	COMPETING CONTINUATION	$610,981
2017	2015	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	16	12/13/2016	NON-COMPETING CONTINUATION	$0
2017	2015	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	002	16	5/12/2017	NON-COMPETING CONTINUATION	-$1,716
														Subtotal = $747,776

Issue Date FY: 2015 ( Subtotal = $724,852 )
2015	2015	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	15	6/26/2015	SUPPLEMENT FOR EXPANSION	$125,000
2015	2015	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	16	6/29/2015	NON-COMPETING CONTINUATION	$599,852
														Subtotal = $724,852

Issue Date FY: 2014 ( Subtotal = $599,852 )
2014	2014	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	15	7/1/2014	NON-COMPETING CONTINUATION	$599,852
														Subtotal = $599,852

Issue Date FY: 2013 ( Subtotal = $578,858 )
2013	2013	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	14	7/18/2013	NON-COMPETING CONTINUATION	$578,858
														Subtotal = $578,858

Issue Date FY: 2012 ( Subtotal = $599,853 )
2012	2012	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	13	8/24/2012	COMPETING CONTINUATION	$599,853
														Subtotal = $599,853

Issue Date FY: 2011 ( Subtotal = $363,421 )
2011	2011	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	12	6/27/2011	NON-COMPETING CONTINUATION	$23,127
2011	2011	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	12	11/30/2010	NON-COMPETING CONTINUATION	$340,294
														Subtotal = $363,421

Issue Date FY: 2010 ( Subtotal = $367,270 )
2010	2010	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	11	11/26/2009	NON-COMPETING CONTINUATION	$333,882
2010	2010	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	11	3/10/2010	NON-COMPETING CONTINUATION	$33,388
														Subtotal = $367,270

Issue Date FY: 2009 ( Subtotal = $360,351 )
2009	2009	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	001	10	3/26/2009	NON-COMPETING CONTINUATION	$36,035
2009	2009	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	10	10/29/2008	NON-COMPETING CONTINUATION	$324,316
														Subtotal = $360,351

Issue Date FY: 2008 ( Subtotal = $350,038 )
2008	2008	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Biomedical Research and Research Training	000	9	12/3/2007	COMPETING CONTINUATION	$350,038
														Subtotal = $350,038

Grand Total All Awards = $11,910,160

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Histone mRNA Regulation in Development

Award Number: R01GM058921

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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