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The molecular and structural basis of glycoRNA-receptor interaction

Award Number: K99GM166994
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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The molecular and structural basis of glycoRNA-receptor interaction - Project Summary RNA has long been confined to the nucleus and cytoplasm, while glycosylation occurs primarily within the endoplasmic reticulum and Golgi apparatus. This spatial separation led to the long-standing assumption that RNA could not be glycosylated. The recent discovery of glycosylated RNAs (glycoRNAs) overturns this paradigm, revealing glycoRNAs are mainly displayed on the cell surface. Despite this breakthrough, the chemical nature, biochemical properties, and physiological functions of glycoRNAs remain largely unknown. My recent studies revealed that neutrophil surface glycoRNAs mediate neutrophil recruitment to inflammatory sites through interaction with endothelial P-selectin. These results provide the first functional evidence for glycoRNAs and identify P-selectin as their first functional receptor. This work uncovers a previously unrecognized layer of cell-surface regulation by RNA-linked glycoconjugates and establishes a physiologically relevant system to dissect the biochemical, structural, and mechanistic principles of glycoRNA–receptor recognition. The long-term goal of my research is to establish glycoRNAs as a new class of extracellular signaling molecules that mediate cell–cell communication, define their biochemical and structural diversity, and elucidate their physiological roles in immunity and inflammation. The objective of this K99/R00 proposal is to determine the chemical, biochemical, and structural bases of glycoRNA–P-selectin interactions, establishing this system as a model to dissect the molecular principles and physiological functions of RNA glycosylation. In Aim 1, I will define the biochemical properties and binding characteristics of glycoRNAs–P-selectin interaction by quantifying kinetic parameters, and the contributions of RNA and glycan moieties. In Aim 2, I will determine the chemical composition of P-selectin–binding glycoRNAs, identifying both RNA templates and glycan structures. By integrating optimized glycoRNA sequencing and glycan mass spectrometry, this work will reveal how RNA sequence/structure, glycan attachment sites, and glycan chemistry determine selective recognition by P-selectin. In Aim 3, I will resolve the three-dimensional architecture of the glycoRNAs–P-selectin complex. If high-resolution experimental structures cannot be obtained, we will perform computational modeling of the glycoRNA–P-selectin complex. I will also generate P-selectin mutants to validate structural determinants of glycoRNA binding and functional consequences in vitro. Collectively, these studies will define the molecular principles of glycoRNAs in recognition by adhesion receptors. By revealing the chemistry, biochemistry, and structural basis of glycoRNAs–P-selectin interactions, this work will provide fundamental insights into how glycoRNAs regulates cell–cell communication and immune cell trafficking, aligning with the NIGMS mission to uncover fundamental molecular mechanisms and supporting me to independence in RNA glycobiology.


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 = $125,000 )
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Biomedical Research and Research Training	000	1	8/21/2026	NEW	$125,000
														Subtotal = $125,000

Grand Total All Awards = $125,000

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The molecular and structural basis of glycoRNA-receptor interaction

Award Number: K99GM166994

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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