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A genomic approach to studying the life cycle of intron lariats

Award Number: R01GM105681
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: 07/16/2014
PERIOD OF PERFORMANCE END DATE: 01/31/2024

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A genomic approach to studying the life cycle of intron lariats - Project Summary/Abstract Pre-mRNA splicing is a critical and regulated processing event where introns are precisely excised from nascent RNA transcripts. As many as one third of all heritable disease mutations result in splicing defects. This research studies the role of branchpoints in determining splice site selection (3'ss) is utilized in vivo and also the effect branchpoints have on the life cycle of the intron. Each pre-mRNA splicing event creates a lariat and spliced exon junction. While a great deal is known about splice exon junctions almost nothing is known about lariats. By mapping all branchpoints in the human genome, we are opening up a whole new area of analysis. The identification of branchpoints by transcript data will facilitate the interpretation of clinical sequencing data. In addition to the intrinsic value of this data, the successful completion of this proposal will test some hypothesis about the fundamental catalysis and recognition that occurs in vivo in the processing of eukaryotic genes. Studying these intermediates at a system wide level will bring a biochemical-level understanding to hundreds of thousands of processing events. Furthermore, each intron lariat has a lifecycle – created by splicing of a transcribed product, recycled by debranching and degradation. The recycling of introns is vital to replenishing the intracellular levels of free nucleotides and to return splicing factors into active spliceosomes. Some introns have a second life after splicing as non- coding RNAs (ncRNAs). As we are sampling steady state levels of introns we gain insight into both these processes. This proposal seeks to follow this lead by exploring some of the reasons why certain introns appear stabilized.


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: 2024 ( Subtotal = -$94,579 )
2024	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	001	8	8/8/2024	SUPPLEMENT FOR EXPANSION	-$21,196
2024	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	8	8/8/2024	NON-COMPETING CONTINUATION	-$73,383
														Subtotal = -$94,579

Issue Date FY: 2022 ( Subtotal = $566,625 )
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	001	8	1/19/2022	SUPPLEMENT FOR EXPANSION	$126,986
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	8	1/18/2022	NON-COMPETING CONTINUATION	$395,675
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	002	8	8/1/2022	NON-COMPETING CONTINUATION	$43,964
														Subtotal = $566,625

Issue Date FY: 2021 ( Subtotal = $617,727 )
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	001	7	1/27/2021	NON-COMPETING CONTINUATION	$533,202
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	002	7	2/23/2021	NON-COMPETING CONTINUATION	$59,246
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	6	11/24/2020	SUPPLEMENT FOR EXPANSION	$25,279
														Subtotal = $617,727

Issue Date FY: 2020 ( Subtotal = $440,503 )
2020	2020	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	6	5/1/2020	NON-COMPETING CONTINUATION	$440,503
														Subtotal = $440,503

Issue Date FY: 2019 ( Subtotal = $440,503 )
2019	2019	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	001	5	1/28/2019	COMPETING CONTINUATION	$440,503
2019	2017	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	002	4	5/23/2019	NON-COMPETING CONTINUATION	$0
2019	2017	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	4	1/23/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $440,503

Issue Date FY: 2017 ( Subtotal = $415,027 )
2017	2017	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	4	3/20/2017	NON-COMPETING CONTINUATION	$373,524
2017	2017	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	001	4	6/14/2017	NON-COMPETING CONTINUATION	$41,503
														Subtotal = $415,027

Issue Date FY: 2016 ( Subtotal = $414,170 )
2016	2016	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	3	3/25/2016	NON-COMPETING CONTINUATION	$414,170
														Subtotal = $414,170

Issue Date FY: 2015 ( Subtotal = $399,909 )
2015	2015	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	2	4/1/2015	NON-COMPETING CONTINUATION	$399,909
														Subtotal = $399,909

Issue Date FY: 2014 ( Subtotal = $417,826 )
2014	2014	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	1	7/16/2014	NEW	$417,826
														Subtotal = $417,826

Grand Total All Awards = $3,617,711

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A genomic approach to studying the life cycle of intron lariats

Award Number: R01GM105681

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: 07/16/2014

PERIOD OF PERFORMANCE END DATE: 01/31/2024

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