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Gene Regulatory Functions for the Nuclear Speckle Protein SON

Award Number: R15GM084407
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: 12/01/2008
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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Gene Regulatory Functions for the Nuclear Speckle Protein SON - Appropriate expression of protein coding genes in mammalian cells requires complex nuclear choreography. Pre-mRNA processing complexes are recruited to transcription sites for capping, splicing and polyadenylation, yielding mature mRNA transcripts for nuclear export (Hirose and Manley, 2000; Lewis and Tollervey, 2000; Bentley 2005). While we understand some details about how RNA polymerase II (RNAPII) initiates transcription at promoters, or how snRNP complexes assemble into spliceosomes at splicing sites, there are gaps in our understanding about how spatiotemporal organization of gene expression within mammalian nuclei is coordinated. Nuclear speckles are domains in nuclei of higher eukaryotes enriched in pre-mRNA processing factors; dynamic exchange permits co-transcriptional pre-mRNA processing (Lamond and Spector, 2003). Our long-term goal is to understand assembly and function of nuclear speckle components and how this impacts pre-mRNA processing. Pinning down nuclear speckle functions has proven to be difficult because they contain at least 180 proteins and an undefined number of noncoding RNAs. Our lab showed that a protein called SON maintains proper organization of pre-mRNA processing factors in nuclear speckles (Sharma et al., 2010). A novel feature of SON is its unique tandem repeats that mediate proper nuclear speckle organization (Sharma et al., 2010). Two new pieces of evidence from our laboratory suggest that SON is also important for gene expression. First, SON is enriched at a facultative heterochromatin gene locus in its silent state, is removed during locus activation, and SON's repeats confer this function. Second, SON is required for appropriate alternative splicing of many gene transcripts. Our hypothesis is that SON influences gene expression via chromatin association as well as pre-mRNA splicing control for a defined subset of protein coding genes. This project aims to define SON-chromatin interactions and to design novel tools to investigate SON-dependent pre-mRNA splicing in situ.


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 = -$12,834 )
2024	2019	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Biomedical Research and Research Training	000	4	11/30/2023	COMPETING CONTINUATION	-$12,834
														Subtotal = -$12,834

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Biomedical Research and Research Training	001	4	3/25/2020	COMPETING CONTINUATION	$3,835
2020	2015	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Biomedical Research and Research Training	000	3	3/25/2020	COMPETING CONTINUATION	-$3,835
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $450,000 )
2019	2019	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Biomedical Research and Research Training	001	4	6/24/2019	COMPETING CONTINUATION	$450,000
2019	2015	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Biomedical Research and Research Training	000	3	6/19/2019	COMPETING CONTINUATION	$0
														Subtotal = $450,000

Issue Date FY: 2015 ( Subtotal = $377,388 )
2015	2015	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Biomedical Research and Research Training	002	3	9/22/2015	COMPETING CONTINUATION	$377,388
2015	2011	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Biomedical Research and Research Training	000	2	5/15/2015	COMPETING CONTINUATION	$0
2015	2011	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Biomedical Research and Research Training	001	2	9/16/2015	COMPETING CONTINUATION	$0
														Subtotal = $377,388

Issue Date FY: 2011 ( Subtotal = $292,000 )
2011	2011	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Biomedical Research and Research Training	001	2	7/18/2011	COMPETING CONTINUATION	$292,000
2011	2009	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Biomedical Research and Research Training	000	1	7/18/2011	NEW	$0
														Subtotal = $292,000

Issue Date FY: 2009 ( Subtotal = $212,640 )
2009	2009	WRIGHT STATE UNIVERSITY	3640 COLONEL GLEN HWY	DAYTON	OH	45435	GREENE	USA	Biomedical Research and Research Training	000	1	11/20/2008	NEW	$212,640
														Subtotal = $212,640

Grand Total All Awards = $1,319,194

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Gene Regulatory Functions for the Nuclear Speckle Protein SON

Award Number: R15GM084407

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: 12/01/2008

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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