Tuesday, September 16, 2025 9/16/2025

RNA Structural Motif Analysis Revisited: Towards a Systematic Understanding of Noncoding RNA as Modular Biomolecules

Award Number: R01GM102515
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: 09/01/2012
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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RNA Structural Motif Analysis Revisited: Towards a Systematic Understanding of Noncoding RNA as Modular Biomolecules - Project Summary Non-coding RNAs (ncRNAs) play crucial roles in catalysis, gene expression regulation, RNA splicing, and various other biological processes. Their functions are facilitated by their unique 3D structures, which include recurrent substructural components known as RNA structural motifs (RSMs). RSMs are conserved in sequence composition, base interaction patterns, and 3D geometry, serving as fundamental building blocks of RNA structure and function. The dysfunction of RSMs has been linked to various diseases, highlighting the importance of studying these motifs to understand RNA-related diseases and develop potential cures. Our previous NIH- funded research established a strong connection between RSMs and their distinctive base interaction patterns (pairing and stacking). We developed computational methods for detecting and clustering RSMs based on these patterns. This interaction pattern-centric approach is more sensitive, allowing for geometrical variation among functional homologs, and faster, as it bypasses the need to superimpose RSMs. However, predicting base interactions remains imperfect, making it challenging to distinguish between function-preserving covariations and annotation errors. To address this, we will develop a more accurate base interaction annotation framework by reframing the problem as a 3D point cloud object detection problem in computer vision. With improved base interaction patterns, we expect to identify more RSM instances from the growing repository of RNA 3D structures in the Protein Data Bank (PDB). This expanded collection will enable the categorization of RSMs, crucial for defining function-determining characteristics and understanding permissible variations in different residues. We propose a de novo clustering method based on similarities in both base interaction patterns and 3D geometry. Additionally, we will develop algorithms to compare RSM families and explore their organizational architecture - whether hierarchical with superfamilies and subfamilies or flat with near-equally distinct families. Using this knowledge, we will quantify RSM family conservations and variations by constructing probabilistic profiles. These profiles will facilitate the detection of RSM-encoding regions in multiple aligned genomic sequences. Coupled with secondary structure information, we will define a novel representation for RNA structure: the RSM-enriched Secondary Structure (RSMe-SS). We hypothesize that RSMe-SS will be informative for functional inference. To support the hypothesis, we will construct a mathematical model connecting RSMe-SS with molecular functions. If successful, this approach could revolutionize medical genomics by enabling reference-independent functional investigation of novel ncRNA biomarkers and SNPs discovered in high-throughput experiments. In summary, we propose an in-depth study of RSM and extend its applications to ncRNA functional inference in sequence data. This project aims to elucidate fundamental RNA structure-function relationships, significantly impacting basic science. It will also advance medical research by extending the scope of medical genomics beyond proteins to include ncRNAs.


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 = $1,119,355 )
2025	2025	THE UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Biomedical Research and Research Training	000	8	9/1/2025	COMPETING CONTINUATION	$1,119,355
														Subtotal = $1,119,355

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	THE UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Biomedical Research and Research Training	000	7	9/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Biomedical Research and Research Training	000	7	3/9/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $173,976 )
2021	2021	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Biomedical Research and Research Training	000	7	3/15/2021	NON-COMPETING CONTINUATION	$173,976
														Subtotal = $173,976

Issue Date FY: 2020 ( Subtotal = $174,561 )
2020	2020	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Biomedical Research and Research Training	000	6	4/1/2020	NON-COMPETING CONTINUATION	$174,561
														Subtotal = $174,561

Issue Date FY: 2019 ( Subtotal = $175,117 )
2019	2019	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Biomedical Research and Research Training	000	5	3/20/2019	NON-COMPETING CONTINUATION	$175,117
														Subtotal = $175,117

Issue Date FY: 2018 ( Subtotal = $175,647 )
2018	2018	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Biomedical Research and Research Training	001	4	4/30/2018	COMPETING CONTINUATION	$175,647
2018	2014	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Biomedical Research and Research Training	000	3	11/27/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $175,647

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2014	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Biomedical Research and Research Training	000	3	7/22/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $168,773 )
2014	2014	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Biomedical Research and Research Training	000	3	8/14/2014	NON-COMPETING CONTINUATION	$168,773
														Subtotal = $168,773

Issue Date FY: 2013 ( Subtotal = $164,019 )
2013	2013	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Biomedical Research and Research Training	000	2	8/20/2013	NON-COMPETING CONTINUATION	$164,019
														Subtotal = $164,019

Issue Date FY: 2012 ( Subtotal = $169,158 )
2012	2012	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Biomedical Research and Research Training	000	1	8/23/2012	NEW	$169,158
														Subtotal = $169,158

Grand Total All Awards = $2,320,606

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RNA Structural Motif Analysis Revisited: Towards a Systematic Understanding of Noncoding RNA as Modular Biomolecules

Award Number: R01GM102515

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: 09/01/2012

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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