Chromatin-associated orphan snoRNA regulates DNA damage-mediated differentiation via a non-canonical complex.

Small nucleolar RNAs (snoRNAs) are commonly acknowledged as a class of homogeneous non-coding RNAs that guide ribosomal RNA modifications. However, snoRNAs referred to as orphans have largely unknown functions. Here, we systematically profile chromatin-associated snoRNAs (casnoRNAs) in mammalian cells and identify a subgroup of orphan casnoRNAs responding to DNA damage stress, among which SNORA73 shows the most marked reduction in chromatin enrichment. Downregulated SNORA73 maintains cancer genome stability and differentiation block in hematopoietic malignancy. Mechanistically, casnoRNA the 5' end non-canonical structure of SNORA73 is critical for its function and binding to poly (ADP-ribose) polymerase 1 (PARP1). SNORA73 inhibits PARP1 auto-PARylation to affect cancer genome stability by forming a small nucleolar ribonucleoprotein (snoRNP) with PARP1 and canonical H/ACA proteins DKC1/NHP2. Our findings reveal the role of an orphan snoRNA serving as casnoRNA and highlights a link between non-canonical structure of snoRNA and their functional diversity.

• Publication year

  2022

• Venue

  Cell Reports

• Publication date

  2022-03-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.celrep.2022.110421PMID 35354054
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• APOBEC3B-mediated corruption of the tumor cell immunopeptidome induces heteroclitic neoepitopes for cancer immunotherapy

  2020cited by this paper
• Site-specific methylation of 18S ribosomal RNA by SNORD42A is required for Acute Myeloid Leukemia cell proliferation.

  2020cited by this paper
• A Nucleolar PARtnership Expands PARP Roles in RNA Biology and the Clinical Potential of PARP Inhibitors.

  2019cited by this paper
• Functional diversity of small nucleolar RNAs

  2019cited by this paper
• Barrier-to-autointegration factor 1 (Banf1) regulates poly [ADP-ribose] polymerase 1 (PARP1) activity following oxidative DNA damage

  2019cited by this paper
• CircMYBL2, a circRNA from MYBL2, Regulates FLT3 Translation by Recruiting PTBP1 to Promote FLT3-ITD AML Progression.

  2019cited by this paper
• Activation of PARP-1 by snoRNAs Controls Ribosome Biogenesis and Cell Growth via the RNA Helicase DDX21.

  2019cited by this paper
• Cooperative 2′-O-methylation of the wobble cytidine of human elongator tRNAMet(CAT) by a nucleolar and a Cajal body-specific box C/D RNP

  2019cited by this paper
• Chromatin-associated RNAs as facilitators of functional genomic interactions

  2019cited by this paper
• Activation of the Lysosome-Associated Membrane Protein LAMP5 by DOT1L Serves as a Bodyguard for MLL Fusion Oncoproteins to Evade Degradation in Leukemia

  2019cited by this paper
• The Human RNA-Binding Proteome and Its Dynamics during Translational Arrest.

  2019cited by this paper
• Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality.

  2018cited by this paper
• Determinants and clinical implications of chromosomal instability in cancer

  2018cited by this paper
• Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors.

  2018cited by this paper
• Long-range function of secreted small nucleolar RNAs that direct 2′-O-methylation

  2018cited by this paper
• Expression profiling of snoRNAs in normal hematopoiesis and AML.

  2018cited by this paper
• Long ncRNA A-ROD activates its target gene DKK1 at its release from chromatin

  2018cited by this paper
• Chromatin RNA Immunoprecipitation (ChRIP).

  2018cited by this paper
• A Pan-cancer Analysis of the Expression and Clinical Relevance of Small Nucleolar RNAs in Human Cancer.

  2017cited by this paper
• APC/C Dysfunction Limits Excessive Cancer Chromosomal Instability.

  2017cited by this paper
• Genomic Instability in Cancer: Teetering on the Limit of Tolerance.

  2017cited by this paper
• A snoRNA modulates mRNA 3′ end processing and regulates the expression of a subset of mRNAs

  2017cited by this paper
• The HSF1–PARP13–PARP1 complex facilitates DNA repair and promotes mammary tumorigenesis

  2017cited by this paper
• Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel.

  2017cited by this paper
• In Situ Capture of Chromatin Interactions by Biotinylated dCas9.

  2017cited by this paper
• Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth

  2017cited by this paper
• Transcriptome-wide identification of the RNA-binding landscape of the chromatin-associated protein PARP1 reveals functions in RNA biogenesis

  2017cited by this paper
• The multifaceted roles of PARP1 in DNA repair and chromatin remodelling

  2017cited by this paper
• An updated human snoRNAome

  2016cited by this paper
• The lncRNA HOTAIRM1 regulates the degradation of PML-RARA oncoprotein and myeloid cell differentiation by enhancing the autophagy pathway

  2016cited by this paper
• Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing

  2016cited by this paper
• The emerging landscape of small nucleolar RNAs in cell biology

  2015cited by this paper
• Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors

  2015cited by this paper
• Cytosolic Accumulation of Small Nucleolar RNAs (snoRNAs) Is Dynamically Regulated by NADPH Oxidase*

  2015cited by this paper
• Nuclear Fractionation Reveals Thousands of Chromatin-Tethered Noncoding RNAs Adjacent to Active Genes.

  2015cited by this paper
• Detection of RNA-Protein Interactions Using Tethered RNA Affinity Capture.

  2015cited by this paper
• Brca1 deficiency causes bone marrow failure and spontaneous hematologic malignancies in mice.

  2015cited by this paper
• Small RNAs with big implications: new insights into H/ACA snoRNA function and their role in human disease

  2015cited by this paper
• Chromosome preparation from cultured cells.

  2014cited by this paper
• DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier

  2014cited by this paper
• Analysis of nuclear RNA interference in human cells by subcellular fractionation and Argonaute loading

  2014cited by this paper
• The dyskerin ribonucleoprotein complex as an OCT4/SOX2 coactivator in embryonic stem cells

  2014cited by this paper
• A Differentiation Checkpoint Limits Hematopoietic Stem Cell Self-Renewal in Response to DNA Damage.

  2014cited by this paper
• Manual hematoxylin and eosin staining of mouse tissue sections.

  2014cited by this paper
• Evf2 (Dlx6as) lncRNA regulates ultraconserved enhancer methylation and the differential transcriptional control of adjacent genes

  2013cited by this paper
• Are snoRNAs and snoRNA host genes new players in cancer?

  2012cited by this paper
• Specific small nucleolar RNA expression profiles in acute leukemia

  2012cited by this paper
• Multiple myeloma-associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress.

  2012cited by this paper
• A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage.

  2012cited by this paper
• The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma

  2012cited by this paper
• Small nucleolar RNAs U32a, U33, and U35a are critical mediators of metabolic stress.

  2011cited by this paper
• Hallmarks of cancer: the next generation.

  2011cited by this paper
• A homologous production system for Trichoderma reesei secreted proteins in a cellulase-free background

  2011cited by this paper
• Strong dependence between functional domains in a dual-function snoRNA infers coupling of rRNA processing and modification events

  2010cited by this paper
• Mutations in maltose-binding protein that alter affinity and solubility properties

  2010cited by this paper
• Evidence of Xist RNA-independent initiation of mouse imprinted X-chromosome inactivation

  2009cited by this paper
• Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation.

  2008cited by this paper
• Genomic instability in myeloid malignancies: increased reactive oxygen species (ROS), DNA double strand breaks (DSBs) and error-prone repair.

  2008cited by this paper
• Transcriptional control by PARP-1: chromatin modulation, enhancer-binding, coregulation, and insulation.

  2008cited by this paper
• DNA repair is limiting for haematopoietic stem cells during ageing

  2007cited by this paper
• Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs.

  2007cited by this paper
• Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age

  2007cited by this paper
• Mfold web server for nucleic acid folding and hybridization prediction

  2003cited by this paper
• Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell maintenance and DNA repair.

  2003cited by this paper
• Function and synthesis of small nucleolar RNAs.

  1997cited by this paper
• Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs.

  1996cited by this paper
• Physical isolation of nascent RNA chains transcribed by RNA polymerase II: evidence for cotranscriptional splicing

  1994cited by this paper
• Disruption of U8 nucleolar snRNA inhibits 5.8S and 28S rRNA processing in the Xenopus oocyte.

  1993cited by this paper
• The U3 small nucleolar ribonucleoprotein functions in the first step of preribosomal RNA processing.

  1990cited by this paper
• U3, U8 and U13 comprise a new class of mammalian snRNPs localized in the cell nucleolus.

  1989cited by this paper

• RBM15B recognizes H3K79me2 to guide selective m6A-modification of mRNA and enhance oncoprotein translation in MLL-r leukemia

  2026cites this paper
• LncRNA SNHG3: a potential biomarker for human diseases

  2026cites this paper
• Dysregulation of the DNA damage response by phosphorothioate antisense oligonucleotides

  2026cites this paper
• Chromatin-Associated RNAs Regulate Gene Expression and Chromatin Structure

  2025cites this paper
• Biological roles and potential clinical values of snoRNAs in Cancer.

  2025cites this paper
• Chromatin-associated circRNA ciCRLF3(2) regulates cell differentiation blockage via activating non-homologous end joining–based DNA repair

  2025influential citation
• Small Nucleolar RNAs: Biological Functions and Diseases

  2025cites this paper
• PARP1: A comprehensive review of its mechanisms, therapeutic implications and emerging cancer treatments.

  2025cites this paper
• Computational limitations and future needs to unravel the full potential of 2’-O-methylation and C/D box snoRNAs

  2025cites this paper
• H/ACA snoRNAs and snoRNPs Dysregulation Links rRNA Modification to Glioblastoma Progression

  2025cites this paper
• Small Nucleolar RNAs as Emerging Players in Cancer Biology and Precision Medicine

  2025cites this paper
• The regulatory roles of small nucleolar RNAs within their host locus

  2024cites this paper
• How snoRNAs can contribute to cancer at multiple levels

  2024cites this paper
• Subverting the Canon: Novel Cancer-Promoting Functions and Mechanisms for snoRNAs

  2024cites this paper
• SnoRNAs in cardiovascular development, function, and disease.

  2024cites this paper
• Advancing NSCLC Diagnosis: The Role of Tumor-Derived Serum Exosomal SNORD60 as a Novel Biomarker

  2024cites this paper
• Small Nucleolar RNAs as Diagnostic and Prognostic Biomarkers in Cancer: A Systematic Review and Meta-Analysis

  2024cites this paper
• Grafting based DNA methylation alteration of snoRNAs in upland cotton (Gossypium L.)

  2024cites this paper
• The landscape of RNA-chromatin interaction reveals small non-coding RNAs as essential mediators of leukemia maintenance

  2024cites this paper
• The zebrafish (Danio rerio) snoRNAome

  2024cites this paper
• SnoRNAs: The promising targets for anti-tumor therapy

  2024cites this paper
• Advances in the mechanism of small nucleolar RNA and its role in DNA damage response

  2024cites this paper
• New ZNHIT3 Variants Disrupting snoRNP Assembly Cause Prenatal PEHO Syndrome with Isolated Hydrops

  2024cites this paper
• SnoRNA and lncSNHG: Advances of nucleolar small RNA host gene transcripts in anti-tumor immunity

  2023cites this paper
• The chromatin-associated RNAs in gene regulation and cancer

  2023cites this paper
• The emerging landscape of non-conventional RNA functions in atherosclerosis.

  2023cites this paper
• METTL3 protects METTL14 from STUB1‐mediated degradation to maintain m6A homeostasis

  2023cites this paper
• Regulation of the epigenome through RNA modifications

  2023cites this paper
• Noncoding RNA-chromatin association: Functions and mechanisms

  2023cites this paper
• Human PARP1 substrates and regulators of its catalytic activity: An updated overview

  2023cites this paper
• New insight into circRNAs: characterization, strategies, and biomedical applications

  2023cites this paper
• Small but strong: the emerging role of small nucleolar RNA in cardiovascular diseases

  2023cites this paper
• Emerging roles of SnoRNAs in the pathogenesis and treatment of autoimmune disorders.

  2023cites this paper
• Transcriptome analyses of mouse cardiac myocytes and non-cardiomyocytes: postmitotic vs. proliferative cells

  2023cites this paper
• Screening and identification of potential biomarkers for pancreatic cancer: An integrated bioinformatics analysis.

  2023cites this paper
• Comprehensive map of ribosomal 2′-O-methylation and C/D box snoRNAs in Drosophila melanogaster

  2023cites this paper
• From molecular basics to agronomic benefits: Insights into noncoding RNA-mediated gene regulation in plants.

  2022cites this paper
• snoRNAs: functions and mechanisms in biological processes, and roles in tumor pathophysiology

  2022cites this paper
• RNA-based mechanisms of chromatin and gene regulation

  year unknowncites this paper