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Biogenesis of mRNA-derived telomerase long noncoding RNA

Award Number: R01GM149864
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: 05/16/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Biogenesis of mRNA-derived telomerase long noncoding RNA - Project Summary Most RNA molecules transcribed in mammalian cells do not encode for protein sequences. Among these noncoding RNAs (ncRNA) is a vast family of long noncoding RNAs (lncRNAs) that are larger than 200 nt. LncRNAs can modulate cellular protein expression patterns by influencing the transcription of many genes, the post-transcriptional fate of mRNAs and ncRNAs, and the turnover and localization of proteins. Telomerase RNA is a unique class of lncRNA that functions as an integral component of the telomerase ribonucleoprotein complex which maintains genomic stability and cellular immortality in cancer and stem cells. The overarching goal of this project is to understand the mechanism and regulation of a novel mRNA-derived biogenesis of telomerase RNA (lncRNA) in Ustilago maydis, a basidiomycete fungus. Telomerase RNA in Ascomycete yeasts and animals, telomerase RNAs are transcribed by RNA polymerase II and share biogenesis pathways with small nuclear RNA (snRNA) and box H/ACA small nucleolar RNA (snoRNA), respectively. In contrast, telomerase RNAs in ciliates and plants are transcribed by RNA polymerase III. These distinct biogenesis mechanisms employed by these homologous telomerase RNA molecules from different eukaryotic kingdoms or groups provide unparalleled opportunities for understanding the fundamental principles underlying the biogenesis and evolution of the vast varieties of noncoding RNA species in biology. We have recently identified the first Basidiomycete telomerase RNA from U. maydis, a fungal model organism. Animal and yeast TRs are transcribed by RNA polymerase II with a protective cap at the 5’-end. intriguingly, the U. maydis TR lacks a protective 5’ cap and is processed from the 3’-untranslated region of a protein-coding mRNA precursor. In this research program, we will identify determinants in the TR precursor that regulate the biogenesis of the mature U. maydis TR from the protein-coding mRNA. We will also study the function and expression of the protein encoded in the mRNA precursor. Lastly, we will identify telomerase accessory proteins in U. maydis and determine their roles in regulating the U. maydis TR biogenesis. Successful outcomes of these specific aims will provide comprehensive and exciting details needed for understanding the unprecedented mRNA-derived biogenesis mechanism of telomerase lncRNA.


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: 2026 ( Subtotal = $309,216 )
2026	2026	ARIZONA STATE UNIVERSITY	1475 N SCOTTSDALE RD STE 200	SCOTTSDALE	AZ	85257	MARICOPA	USA	Biomedical Research and Research Training	000	4	4/2/2026	NON-COMPETING CONTINUATION	$309,216
														Subtotal = $309,216

Issue Date FY: 2025 ( Subtotal = $310,152 )
2025	2025	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	001	3	8/29/2025	NON-COMPETING CONTINUATION	$31,015
2025	2025	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	000	3	3/25/2025	NON-COMPETING CONTINUATION	$279,137
														Subtotal = $310,152

Issue Date FY: 2024 ( Subtotal = $311,018 )
2024	2024	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	000	2	3/21/2024	NON-COMPETING CONTINUATION	$279,916
2024	2024	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	001	2	6/10/2024	NON-COMPETING CONTINUATION	$31,102
														Subtotal = $311,018

Issue Date FY: 2023 ( Subtotal = $302,473 )
2023	2023	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	000	1	5/16/2023	NEW	$302,473
														Subtotal = $302,473

Grand Total All Awards = $1,232,859

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Biogenesis of mRNA-derived telomerase long noncoding RNA

Award Number: R01GM149864

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: 05/16/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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