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Non-coding RNA regulation of neuronal protein translation and appetite control

Award Number: F31HD113399
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/30/2023
PERIOD OF PERFORMANCE END DATE: 05/28/2026
AWARD TERMINATION DATE: 08/01/2026

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Non-coding RNA regulation of neuronal protein translation and appetite control - ABSTRACT Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder with no cure. Individuals with PWS exhibit feeding difficulties and failure-to-thrive in infancy followed by an insatiable appetite and hyperphagia in adulthood. The smallest deletions known to cause PWS involve a paternally expressed cluster of neuron-specific small nucleolar RNAs (snoRNAs), Snord116. The molecular targets and functions of Snord116 are not known. Snord116 is highly expressed in brain regions critical for appetite control, but how Snord116 loss affects the activity of appetite-regulating neurons is also not known. To determine how Snord116 loss alters feeding behavior, it is critical to determine the molecular and cellular functions of Snord116 in appetite-regulating neurons. Most snoRNAs play well conserved roles in ribosome biogenesis and are ubiquitously expressed across tissues. Snord116, uniquely, is preferentially expressed in neurons. Neurons have unique translational demands due to their size and complexity, and neuronal ribosomes have specialized properties to meet those demands. It is not known if Snord116 may contribute to neuron-specific aspects of ribosome biogenesis or protein translation. Therefore, I will investigate the effect of Snord116 loss on neuronal protein translation in parts of the brain known to control appetite. Additionally, I will determine the effect of Snord116 loss on the activity of appetite-regulating neurons and how dysfunction of these neurons may underlie hyperphagia. By delineating the molecular function of a neuron-specific snoRNA, I expect to broadly contribute toward a better understanding of how protein translation is regulated in neurons. Conducting these studies in a relevant population of appetite- regulating neurons also allows us to examine the role of snoRNAs and translation in proper control of feeding circuits in the brain. The insights gained into the molecular basis of appetite control will better inform not only potential therapies for PWS but also obesity, an increasingly prevalent health problem among children.


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 = -$9,595 )
2026	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	000	3	8/1/2026	TERMINATION	-$9,595
														Subtotal = -$9,595

Issue Date FY: 2025 ( Subtotal = $37,482 )
2025	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	000	3	9/5/2025	NON-COMPETING CONTINUATION	$37,482
														Subtotal = $37,482

Issue Date FY: 2024 ( Subtotal = $36,918 )
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	000	2	8/9/2024	NON-COMPETING CONTINUATION	$36,918
														Subtotal = $36,918

Issue Date FY: 2023 ( Subtotal = $41,923 )
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	000	1	8/17/2023	NEW	$41,923
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Child Health and Human Development Extramural Research	001	1	8/17/2023	NEW	$0
														Subtotal = $41,923

Grand Total All Awards = $106,728

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Non-coding RNA regulation of neuronal protein translation and appetite control

Award Number: F31HD113399

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/30/2023

PERIOD OF PERFORMANCE END DATE: 05/28/2026

AWARD TERMINATION DATE: 08/01/2026

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