Subverting the Canon: Novel Cancer-Promoting Functions and Mechanisms for snoRNAs - academic review

Sep 21, 2026

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Small nucleolar RNAs (snoRNAs) are intron-derived non-coding RNAs (about 60–300 nucleotides) that are canonically localized in the nucleolus, where they regulate RNA modifications and pre-ribosomal RNA processing. They are typically grouped into box C/D and H/ACA families, mediating methylation and pseudouridylation. Emerging findings show unconventional snoRNA biogenesis and roles in disease, prompting this review to synthesize new mechanistic insights into snoRNA-driven cancer. The article highlights snoRNA signaling-pathway interactions, considers therapeutic implications, and discusses lncSNHG as a snoRNA-generating subset of lncRNAs, along with the nucleolus as the functional hub. By deconstructing snoRNA-induced oncogenesis pathways, it aims to guide future snoRNA–cancer research and inform snoRNA-based therapies.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages32

Reading Time1 h 21 min

AccessFree to download

Introduction

Canonical roles of snoRNAs in nucleolar RNA processing

Non-canonical mechanisms linking snoRNAs to disease

Orphan snoRNAs and stress-responsive casnoRNAs

snoRNA-derived fragments and gene regulation

Review Subverting the Canon: Novel Cancer-Promoting Functions and Mechanisms for snoRNAs Matthew Huo 1,2, Sudhir Kumar Rai 2, Ken Nakatsu 2,3, Youping Deng 2, * and Mayumi Jijiwa 2, * Citation: Huo, M.; Rai, S.K.; Nakatsu, K.; Deng, Y.; Jijiwa, M. Subverting the Canon: Novel Cancer-Promoting Functions and Mechanisms for snoRNAs. Int. J. Mol. Sci. 2024, 25, 2923. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms25052923 Academic Editors: Aldo Galeone, Veronica Esposito and Antonella Virgilio Received: 18 January 2024 Revised: 27 February 2024 Accepted: 27 February 2024 Published: 2 March 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218, USA; [mhuo3@jh.edu](mhuo3@jh.edu) [2](2 Department of Quantitative Health Sciences)[ Department of Quantitative Health Sciences](2 Department of Quantitative Health Sciences), [John A](John A). Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA; [raisk21@hawaii.edu](raisk21@hawaii.edu) (S.K.R.); [knakats@emory.edu](knakats@emory.edu) (K.N.) 3 Emory College of Arts and Sciences, Emory University, Atlanta, GA 30322, USA * Correspondence: [dengy@hawaii.edu](dengy@hawaii.edu) (Y.D.); [jijiwa@hawaii.edu](jijiwa@hawaii.edu) (M.J.); Tel.: +1-808-692-1664 (Y.D.);+1-808-692-1670 (M.J.) Abstract: Small nucleolar RNAs (snoRNAs) constitute a class of intron-derived non-coding RNAs ranging from 60 to 300 nucleotides. Canonically localized in the nucleolus, snoRNAs play a pivotal role in RNA modiﬁcations and pre-ribosomal RNA processing. Based on the types of modiﬁcations they involve, such as methylation and pseudouridylation, they are classiﬁed into two main families—box C/D and H/ACA snoRNAs. Recent investigations have revealed the unconventional synthesis and biogenesis strategies of snoRNAs, indicating their more profound roles in pathogenesis than previously envisioned. This review consolidates recent discoveries surrounding snoRNAs and provides insights into their mechanistic roles in cancer. It explores the intricate interactions ofsnoRNAs within signaling pathways and speculates on potential therapeutic solutions emerging from snoRNA research. In addition, it presents recent ﬁndings on the long non-coding small nucleolar RNA host gene (lncSNHG), a subset of long non-coding RNAs (lncRNAs), which are the transcripts of parental SNHGs that generate snoRNA. The nucleolus, the functional epicenter of snoRNAs, is also discussed. Through a deconstruction of the pathways driving snoRNA-induced oncogenesis, this review aims to serve as a roadmap to guide future research in the nuanced ﬁeld of snoRNA–cancer interactions and inspire potential snoRNA-related cancer therapies. Keywords: snoRNA; ribosome; nucleolus; rRNA; SNHG; cancer 1. Introduction The intracellular orchestra of protein synthesis unfolds through a delicate interplay involving small nucleolar RNAs (snoRNAs), small nucleolar RNA host genes (SNHGs), ribosomal RNAs (rRNAs), the nucleolus, and ribosomes. SnoRNAs, derived from speciﬁc genomic loci such as SNHGs, intricately direct the modiﬁcation and processing of rRNAs within the nucleolus. Mature rRNA forms the architectural backbone of ribosomes, the molecular machines that translate genetic information into functional proteins. In recent years, snoRNAs and their associated factors have attracted growing attention. Numerous publications have revealed that these elements are individually or collectively implicated in various human diseases, including cancer, to a greater extent than previously believed. SnoRNAs are c

FAQs

What are snoRNAs and where are they typically localized?

SnoRNAs are intron-derived non-coding RNAs (about 60–300 nucleotides). They are canonically localized in the nucleolus and participate in RNA modifications and pre-ribosomal RNA processing.

How are snoRNAs classified and what canonical functions do they perform?

They are commonly classified into box C/D and H/ACA snoRNA families. These families guide methyltransferase and pseudouridine synthase activities to RNA modification sites via complementary base pairing with target rRNAs.

What non-canonical roles and cancer-related mechanisms does the review emphasize?

The review describes unconventional synthesis/biogenesis of snoRNAs and additional mechanisms beyond nucleolar RNA modification, including roles in piRNA and snoRNA-derived fragments (sdRNAs), miRNA-like regulation, tRNA methylation, rRNA acetylation, splicing regulation, and chromatin accessibility. It also discusses how snoRNA interactions within signaling pathways may contribute to oncogenesis and suggests potential therapeutic directions.

Sep 21, 2026

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