Monday, September 15, 2025 9/15/2025

A non-canonical role for EZH2 in rRNA methtlation

Award Number: R01CA256741
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

Group Awards By:

View Award Description

A non-canonical role for EZH2 in rRNA methtlation - Background: Mounting evidence suggests that dysregulated epigenetic modifications play a crucial role in cancer initiation, progression, and metastasis. Epigenetic regulations include histone modifications, DNA methylation and demethylation, regulations through microRNA and long non-coding RNAs (lncRNAs), and RNA methylation and editing. RNA methylation occurs on all messenger RNA (mRNA), transfer RNA (tRNA) and ribosome RNA (rRNA). Compared to the recent advances in understanding mRNA methylation, the function of rRNA methylation is understudied. The epigenetic modifier Polycomb group protein EZH2, a well-known oncogenic histone lysine methyltransferase for H3K27 methylation and a key component of Polycomb Repressive Complex 2 (PRC2), is upregulated in cancer and is a biomarker of aggressive cancers. Our preliminary data show that EZH2 directly interacts with FBL (Fibrillarin), the only characterized rRNA 2’-O-ribose methyltransferase, and regulates rRNA 2’-O-methylation levels. Knocking down EZH2 alters FBL-mediated nascent peptide synthesis, IRES-driven protein translation initiation, and other ribosomal functions. Importantly, our data reveal that FBL is upregulated in PCa, and EZH2highFBLhigh PCa patients had worse clinic outcomes compared to other patients. Objective/Hypothesis: Our overall hypotheses are that EZH2 plays dual roles in PCa, a canonical role as histone methyltransferase and a non-canonical role by directly interacting with FBL and then regulating rRNA methylation and ribosomal functions. Further, this novel EZH2 function is independent of the PRC2 complex and its lysine methyltransferase activity. Overexpression of EZH2 and FBL together will promote PCa progression. Based on our preliminary data, we propose the following specific aims to test our hypotheses. Specific Aim 1: To investigate how EZH2 regulates the assembly of box C/D snoRNP. Specific Aim 2: To characterize the non-canonical functions of EZH2 in rRNA methylation and protein synthesis through its interaction with FBL in vitro. Specific Aim 3: To examine the EZH2-FBL interaction and EZH2’s novel functions in vivo. Impact: This work will dissect how EZH2 performs its dual role in cancer progression through its canonical function as a H3K27 methyltransferase and a non-canonical function in rRNA methylation via FBL.


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 = $428,722 )
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	000	5	7/23/2025	NON-COMPETING CONTINUATION	$428,722
														Subtotal = $428,722

Issue Date FY: 2024 ( Subtotal = $407,287 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	000	4	6/11/2024	NON-COMPETING CONTINUATION	$407,287
														Subtotal = $407,287

Issue Date FY: 2023 ( Subtotal = $420,147 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	000	3	6/20/2023	NON-COMPETING CONTINUATION	$420,147
														Subtotal = $420,147

Issue Date FY: 2022 ( Subtotal = $420,147 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	000	2	7/19/2022	NON-COMPETING CONTINUATION	$420,147
														Subtotal = $420,147

Issue Date FY: 2021 ( Subtotal = $469,932 )
2021	2021	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Cancer Biology Research	000	1	7/9/2021	NEW	$469,932
														Subtotal = $469,932

Grand Total All Awards = $2,146,235

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A non-canonical role for EZH2 in rRNA methtlation

Award Number: R01CA256741

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/15/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer