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Regulation of microRNA Strand Selection in Caenorhabditis elegans

Award Number: F32GM148040
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 08/08/2022
PERIOD OF PERFORMANCE END DATE: 08/07/2024

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Regulation of microRNA Strand Selection in Caenorhabditis elegans - Project Summary/Abstract Precise control of gene expression programs is critical to maintain cellular homeostasis and ensure normal animal development. Improper gene expression is associated with numerous human pathologies, highlighting the importance of regulated gene expression. microRNAs (miRNAs) are key regulators of eukaryotic gene expression. Although more than half of all human mRNAs are predicted targets of miRNAs, our understanding of how miRNA-meditated gene repression is achieved remains incomplete. A critical step of miRNA-dependent gene regulation is the processing of stem-loop miRNA precursors into double-stranded miRNA duplexes. Each miRNA duplex comprises two strands destined for different fates: one strand is loaded into an Argonaute effector protein to form the miRNA-induced silencing complex (miRISC), while the other strand is degraded. As either miRNA strand can be functional, the decision of which miRNA strand is loaded into Argonaute effectively determines the target repertoire of miRISC. Improper miRNA strand choice can have severe consequences, as alternative miRNA strand selection has been observed in numerous human diseases including atrial fibrillation, multiple sclerosis, and several cancers. The objective of this proposal is to investigate the regulatory mechanisms of miRNA strand selection in vivo using the genetically amenable C. elegans model system. I will establish the hierarchy of miRNA duplex intrinsic and extrinsic features towards the regulation of miRNA strand selection. My central hypothesis is that external regulatory factors can override nucleotide sequence cues to regulate miRNA strand selection in a ‘switch-like’ fashion. Overall, completion of this proposal will significantly expand our understanding of how miRNA strand selection is regulated in the complex context of a developing organism. These findings should provide fundamental insights necessary to understand how miRNA strand selection becomes disrupted in human disease.


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 = -$4,455 )
2025	2023	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	000	2	6/25/2025	NON-COMPETING CONTINUATION	-$4,455
														Subtotal = -$4,455

Issue Date FY: 2023 ( Subtotal = $72,642 )
2023	2023	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	000	2	7/31/2023	NON-COMPETING CONTINUATION	$72,642
														Subtotal = $72,642

Issue Date FY: 2022 ( Subtotal = $67,582 )
2022	2022	KANSAS STATE UNIVERSITY	2 FAIRCHILD HALL	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	000	1	8/5/2022	NEW	$67,582
														Subtotal = $67,582

Grand Total All Awards = $135,769

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Regulation of microRNA Strand Selection in Caenorhabditis elegans

Award Number: F32GM148040

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 08/08/2022

PERIOD OF PERFORMANCE END DATE: 08/07/2024

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