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Regulation of mRNA translation by cis-acting sequences and trans-acting factors

Award Number: R35GM145317
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: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Regulation of mRNA translation by cis-acting sequences and trans-acting factors - While the regulation of gene expression is well recognized as being important to human disease, there is a fundamental gap in understanding the role of post-transcriptional processes. Because post-transcriptional processes are critical for the regulation of protein production, addressing this knowledge gap will facilitate better models of the relationship between genotype and phenotype. Like transcription, mRNA translation is regulated by cis-acting sequences and trans-acting factors. upstream Open Reading Frames (uORFs) are cis-acting regulatory element found in most human genes, and some disease-linked mutations appear to alter the presence of uORFs. The primary focus of my laboratory is to determine how cis-acting sequences and trans-acting factors control translation. Our goal for the next funding period is to determine the functions of human uORFs and evaluate their regulation by trans-acting RNA binding proteins (RBPs). To accomplish this, we have adapted our yeast Massively Parallel Reporter Assays (MPRAs) for use in human tissue culture. In addition, our computational analysis has identified thousands of primate-conserved human uORFs, many of which have conserved RBP binding sites downstream of their start codons. The vast majority of these uORFs have not been functionally studied. Our innovative approach combines exquisite systems biology tools with cutting-edge computational modeling to investigate the functions of these ubiquitous cis-regulatory elements. The proposed research is significant because it is expected to fundamentally advance our understanding of human gene regulation.


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 = $365,148 )
2025	2025	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	4	4/21/2025	NON-COMPETING CONTINUATION	$365,148
2025	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	3	11/22/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $365,148

Issue Date FY: 2024 ( Subtotal = $429,920 )
2024	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	002	3	9/6/2024	SUPPLEMENT FOR EXPANSION	$64,772
2024	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	3	4/3/2024	NON-COMPETING CONTINUATION	$328,634
2024	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	3	7/16/2024	NON-COMPETING CONTINUATION	$36,514
														Subtotal = $429,920

Issue Date FY: 2023 ( Subtotal = $365,148 )
2023	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	2	4/19/2023	NON-COMPETING CONTINUATION	$365,148
														Subtotal = $365,148

Issue Date FY: 2022 ( Subtotal = $365,148 )
2022	2022	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	1	4/29/2022	NEW	$365,148
														Subtotal = $365,148

Grand Total All Awards = $1,525,364

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Regulation of mRNA translation by cis-acting sequences and trans-acting factors

Award Number: R35GM145317

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: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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