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RNA and Genomic Junk in Fundamental Chromosome Architecture and Regulation

Award Number: R35GM122597
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: 06/01/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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RNA and Genomic Junk in Fundamental Chromosome Architecture and Regulation - Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. This project has potential to illuminate a very large but poorly understood component of the human genome, as we seek to find meaningful information in non-coding, repeat-rich sequence, the bulk of our genomes. Emerging evidence shows that much of the non-coding genome is expressed, but often at low levels. A few clearly functional long non-coding RNAs (lncRNAs) are known, yet it remains unclear whether thousands of other low-level, mostly nuclear, lncRNAs are functionally relevant. Based on much progress in the current cycle, we are primed to further advance a broad, impactful hypothesis for how “junk RNAs” may collectively contribute to genome regulation. Our recent work suggests that many long repeat rich (Cot-1) RNAs (including lncRNAs and introns/pre-mRNAs), are not just “products”, but serve essentially as dynamic components of open euchromatin structure. This current MIRA grant represents the convergence of two previously separate projects, one which focused on the long non-coding XIST RNA which transforms an active X-chromosome to a condense heterochromatic Barr Body, and the other focused on nuclear organization of active genes. However, our insights increasingly indicated there was a telling dichotomy between the two, unified by the hypothesis that XIST RNA is not a special example of RNA that impacts chromosome architecture, but exemplifies a much broader aspect of genome/chromosome biology. Rather than XIST RNA simply tethered to chromatin to modify histones, our findings support that XIST RNA also functions to directly modify components of an “RNP-scaffold” that influences the heterochromatin versus euchromatic state. Other recent evidence suggests the RNP-scaffold may be disrupted in certain disease states. As we investigate RNA involvement in chromosome structure at the sequence level, we will seek to connect that to an overall vision of how chromosomes are organized at a much larger scale, and coordinately regulated through development. These ambitious goals will be bolstered by a strong collaborative team, with Dr. Zhiping Weng and Dr. Daryl Bosco.


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 = $558,790 )
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	001	8	1/15/2025	NON-COMPETING CONTINUATION	$558,790
2025	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	7	11/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $558,790

Issue Date FY: 2024 ( Subtotal = $620,878 )
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	003	7	6/26/2024	NON-COMPETING CONTINUATION	$62,088
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	002	7	1/11/2024	NON-COMPETING CONTINUATION	$558,790
2024	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	001	6	12/14/2023	COMPETING CONTINUATION	$261,549
2024	2021	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	5	12/14/2023	NON-COMPETING CONTINUATION	-$261,549
														Subtotal = $620,878

Issue Date FY: 2023 ( Subtotal = $628,366 )
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	001	6	1/26/2023	COMPETING CONTINUATION	$628,366
2023	2021	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	5	1/25/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $628,366

Issue Date FY: 2021 ( Subtotal = $598,444 )
2021	2021	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	5	5/18/2021	NON-COMPETING CONTINUATION	$598,444
														Subtotal = $598,444

Issue Date FY: 2020 ( Subtotal = $598,444 )
2020	2020	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	4	5/29/2020	NON-COMPETING CONTINUATION	$598,444
														Subtotal = $598,444

Issue Date FY: 2019 ( Subtotal = $598,444 )
2019	2019	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	3	5/21/2019	NON-COMPETING CONTINUATION	$598,444
														Subtotal = $598,444

Issue Date FY: 2018 ( Subtotal = $598,444 )
2018	2018	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	2	5/30/2018	NON-COMPETING CONTINUATION	$598,444
														Subtotal = $598,444

Issue Date FY: 2017 ( Subtotal = $378,221 )
2017	2017	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Biomedical Research and Research Training	000	1	5/29/2017	NEW	$378,221
														Subtotal = $378,221

Grand Total All Awards = $4,580,031

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RNA and Genomic Junk in Fundamental Chromosome Architecture and Regulation

Award Number: R35GM122597

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: 06/01/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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