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Elucidation of Integrator's Function

Award Number: R01GM078455
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: 08/01/2010
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Elucidation of Integrator's Function - Project Summary Integrator is a multi-protein complex stably associated with the C-terminal domain (CTD) of RNA polymerase II (RNAPII). Integrator contains a catalytic RNA endonuclease subunit (INTS11) with high degree of homology to cleavage and polyadenylation specificity factor 73 (CPSF73), the enzyme responsible for cleavage and termination of messenger RNA (mRNA) genes. We showed that Integrator RNA processing activity is not only required for noncoding genes but also for protein coding genes facilitating transcriptional elongation. In this proposal, Aim 1; Will detail the mechanism of the Integrator regulation of 3’-end processing and termination of protein coding genes. In Aim 2; We will explore the role of the Integrator complex in regulation of inflammatory gene expression program following our discovery of cooperative association of Integrator with RELA, a component of canonical NFkB complex. These findings expand the role for Integrator in stress signaling and immune system. Finally, in Aim 3; We will elucidate the function of a new trimeric complex composed of INTS11-INTS9 and BRAT1 protein, a gene mutated in human developmental syndromes causing rigidity and multifocal seizure syndrome in neonates and neurodevelopmental disorders.


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 = $447,858 )
2025	2025	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Biomedical Research and Research Training	000	13	5/19/2025	NON-COMPETING CONTINUATION	$447,858
														Subtotal = $447,858

Issue Date FY: 2024 ( Subtotal = $447,858 )
2024	2024	UNIVERSITY OF MIAMI	1320 S DIXIE HWY STE 1200	CORAL GABLES	FL	33146	MIAMI-DADE	USA	Biomedical Research and Research Training	000	12	5/17/2024	NON-COMPETING CONTINUATION	$447,858
														Subtotal = $447,858

Issue Date FY: 2023 ( Subtotal = $447,858 )
2023	2023	UNIVERSITY OF MIAMI	1400 NW 10TH AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	000	11	5/16/2023	NON-COMPETING CONTINUATION	$447,858
														Subtotal = $447,858

Issue Date FY: 2022 ( Subtotal = $447,858 )
2022	2022	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	000	10	8/12/2022	COMPETING CONTINUATION	$447,858
														Subtotal = $447,858

Issue Date FY: 2021 ( Subtotal = -$5,353 )
2021	2019	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	000	9	5/30/2021	NON-COMPETING CONTINUATION	-$5,353
														Subtotal = -$5,353

Issue Date FY: 2019 ( Subtotal = $434,812 )
2019	2019	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	000	9	1/31/2019	NON-COMPETING CONTINUATION	$434,812
														Subtotal = $434,812

Issue Date FY: 2018 ( Subtotal = $441,031 )
2018	2018	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	000	8	11/22/2017	NON-COMPETING CONTINUATION	$396,928
2018	2018	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	001	8	6/22/2018	NON-COMPETING CONTINUATION	$44,103
														Subtotal = $441,031

Issue Date FY: 2017 ( Subtotal = $447,073 )
2017	2017	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	001	7	6/12/2017	NON-COMPETING CONTINUATION	$44,707
2017	2017	UNIVERSITY OF MIAMI	1600 NW 10 AVE	MIAMI	FL	33136	MIAMI-DADE	USA	Biomedical Research and Research Training	000	7	12/20/2016	NON-COMPETING CONTINUATION	$402,366
														Subtotal = $447,073

Issue Date FY: 2016 ( Subtotal = $452,826 )
2016	2016	UNIVERSITY OF MIAMI	P.O. BOX 248106	CORAL GABLES	FL	33124	MIAMI-DADE	USA	Biomedical Research and Research Training	000	6	12/30/2015	COMPETING CONTINUATION	$452,826
														Subtotal = $452,826

Issue Date FY: 2014 ( Subtotal = $21,400 )
2014	2013	UNIVERSITY OF MIAMI	P.O. BOX 248106	CORAL GABLES	FL	33124	MIAMI-DADE	USA	Biomedical Research and Research Training	001	5	6/17/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$61,400
2014	2013	UNIVERSITY OF MIAMI	POST OFFICE BOX 248106	CORAL GABLES	FL	33124	MIAMI-DADE	USA	Biomedical Research and Research Training	002	5	9/10/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2014	2013	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	4	6/17/2014	NON-COMPETING CONTINUATION	-$40,000
														Subtotal = $21,400

Issue Date FY: 2013 ( Subtotal = $378,655 )
2013	2013	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	4	7/31/2013	NON-COMPETING CONTINUATION	$378,655
														Subtotal = $378,655

Issue Date FY: 2012 ( Subtotal = $386,457 )
2012	2012	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	3	7/16/2012	NON-COMPETING CONTINUATION	$386,457
														Subtotal = $386,457

Issue Date FY: 2011 ( Subtotal = $386,457 )
2011	2011	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	2	7/28/2011	NON-COMPETING CONTINUATION	$386,457
														Subtotal = $386,457

Issue Date FY: 2010 ( Subtotal = $390,455 )
2010	2010	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Biomedical Research and Research Training	000	1	7/26/2010	NEW	$390,455
														Subtotal = $390,455

Grand Total All Awards = $5,125,245

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Elucidation of Integrator's Function

Award Number: R01GM078455

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: 08/01/2010

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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