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Probing the Function of Long Non-Coding RNAs in Differentiation

Award Number: R35GM131833
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: 08/20/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Probing the Function of Long Non-Coding RNAs in Differentiation - PROJECT SUMMARY The over-arching focus of my research program has been to identify spatial and temporal aspects of regulating gene expression. Our recent emphasis has incorporated mouse embryonic stem cells (ESCs) as a model system to understand gene dynamics and various aspects of gene expression, including the role of long non- coding RNAs (lncRNAs). LncRNAs represent an exciting class of tens of thousands of RNAs among which very few have thus far been functionally characterized. A number of lncRNAs have been shown to exhibit cell- type specific expression, localization to subcellular compartments, and association with human diseases suggesting that they have critical roles in many cellular processes. The long-term goal of this project is to identify the mechanism of action of several lncRNAs identified in an RNA-seq screen that have roles in pluripotency and/or differentiation, and potentially represent different functional classes, Such analysis will provide insight into how these lncRNAs regulate differentiation through their impacts on gene expression and/or nuclear organization. Here, we propose to characterize an exciting nuclear-retained lncRNA, Platr4, that is highly expressed in pluripotent ESCs and is significantly down-regulated upon ESC differentiation. We will examine the impact of Platr4 knockout and over-expression on global gene expression in ESCs. In addition, Platr4 expression will be examined throughout embryonic development and the impact of Platr4 knockout will be examined in developing mouse embryos to identify critical points of function and candidate genes and pathways regulated by Platr4 in early mouse development. Based upon preliminary studies, the role of Platr4 in mesodermal and endodermal lineage commitment will be an immediate focus of investigation. The functional interactions of Platr4 will be identified by an RNA-tagging strategy combined with RNA-seq (ChIRP-seq) to identify genomic interactions of Platr4, and with mass spectrometry (ChIRP-MS) in order to identify proteins interacting with Platr4. Together, the proposed studies will provide important insights into the functional role of Platr4 in lineage commitment and differentiation, and will provide new insights as to how regulatory signals instructed by a long non-coding RNA can impact differentiation and potentially reprogramming.


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 = $791,040 )
2025	2025	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPG HBR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	001	6	5/22/2025	COMPETING CONTINUATION	$791,040
2025	2023	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPG HBR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	5	11/8/2024	NON-COMPETING CONTINUATION	$0
2025	2023	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPG HBR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	002	5	6/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $791,040

Issue Date FY: 2023 ( Subtotal = $768,000 )
2023	2023	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	5	7/13/2023	NON-COMPETING CONTINUATION	$768,000
														Subtotal = $768,000

Issue Date FY: 2022 ( Subtotal = $768,000 )
2022	2022	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	4	6/23/2022	NON-COMPETING CONTINUATION	$768,000
														Subtotal = $768,000

Issue Date FY: 2021 ( Subtotal = $768,000 )
2021	2021	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	3	7/7/2021	NON-COMPETING CONTINUATION	$768,000
														Subtotal = $768,000

Issue Date FY: 2020 ( Subtotal = $768,000 )
2020	2020	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	2	7/27/2020	NON-COMPETING CONTINUATION	$768,000
														Subtotal = $768,000

Issue Date FY: 2019 ( Subtotal = $768,000 )
2019	2019	COLD SPRING HARBOR LABORATORY	1 BUNGTOWN RD	COLD SPRING HARBOR	NY	11724	SUFFOLK	USA	Biomedical Research and Research Training	000	1	8/20/2019	NEW	$768,000
														Subtotal = $768,000

Grand Total All Awards = $4,631,040

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Probing the Function of Long Non-Coding RNAs in Differentiation

Award Number: R35GM131833

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: 08/20/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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