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Revealing the Regulation of Circular RNA Translation Remodeling Under Stress Conditions

Award Number: R35GM165632
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: 09/08/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

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Revealing the Regulation of Circular RNA Translation Remodeling Under Stress Conditions - PROJECT SUMMARY Stress-induced proteomic remodeling is an essential mechanism that enables cellular adaptation and survival under stress conditions. Importantly, protein expression changes are often regulated at the level of translation, which does not always correlate with transcriptional level. Thus, to fully understand how cells respond to stress, it is crucial to define the regulatory components and mechanisms governing RNA translation. While mRNAs are the primary source of protein synthesis under normal conditions, their translation is globally suppressed during stress, underscoring the need for alternative templates. Circular RNAs (circRNAs), translated via cap-independent initiation, are uniquely suited to fill this role, as their translation is often enhanced under stress. Emerging evidence suggests that stress-induced upregulation of circRNA-encoded proteins can promote cell survival, yet the molecular mechanisms driving this process remain largely unexplored. In this proposal, we will leverage hypoxic stress as a model and apply RAPPL-RiboSeq, a circRNA-compatible ribosome profiling technology we developed, to (i) uncover the regulatory components and mechanisms that facilitate circRNA- specific translational upregulation; (ii) characterize the functional roles of circRNA-encoded proteins during stress; and (iii) reveal genome-wide circRNA translatome remodeling in response to stress. Together, these studies will uncover novel non-canonical molecular players in stress response pathways and stress-related disease pathogenesis, extending beyond the canonical mRNA-encoded proteome and opening new avenues for therapeutic discovery.


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 = $427,625 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Biomedical Research and Research Training	000	1	9/8/2026	NEW	$427,625
														Subtotal = $427,625

Grand Total All Awards = $427,625

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Revealing the Regulation of Circular RNA Translation Remodeling Under Stress Conditions

Award Number: R35GM165632

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: 09/08/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

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