ArticleNucleic acids research2020
Human REXO2 controls short mitochondrial RNAs generated by mtRNA processing and decay machinery to prevent accumulation of double-stranded RNA.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 38 citations in OpenAlex.
- Mitochondrial DNA homeostasis: A novel therapeutic target for neurodegenerative diseases.Neural regeneration research · 2026Article
- Immune response to DNA and RNA: structural insights, molecular mechanisms, and therapeutic targeting.Molecular biomedicine · 2026Review
- Folding the message: mRNA structure as a regulatory layer of human mitochondrial gene expression.Biochimica et biophysica acta. Molecular cell research · 2026Review
- Dysregulated 3'-end processing of 18S pre-rRNA decreases mtPNPase efficiency in plant mitochondria.Nucleic acids research · 2026Article
- Mitochondrial RNA degradation regulates differentiation, stemness, and immune sensitivity in acute myeloid leukemia.Nature communications · 2026Article
- R-loop processing via REXO4-RNaseH1-mediated endo- and exo-cleavage coupling mode prevents genome instability and antitumor immunity.Science advances · 2026Article
- Analysis of Endogenously Expressed Double-Stranded RNAs in Human Cultured Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Identification of alternative splicing events in cows with A1A1 and A2A2 β-casein genotypes using large gap read mapping.BMC genomics · 2025Article
- HIV-associated non-Hodgkin lymphoma tumor-microenvironment axes differ by EBV status across cellular origins.bioRxiv : the preprint server for biology · 2025Article
- The role of four ERS-related key genes in sepsis induced organ dysfunction and the forewarning model construction.BMC medical informatics and decision making · 2025Article
- Transcription, Maturation and Degradation of Mitochondrial RNA: Implications for Innate Immune Response.Biomolecules · 2025Review
- Mitochondrially Transcribed dsRNA Mediates Manganese-induced Neuroinflammation.bioRxiv : the preprint server for biology · 2025Article
- Capsaicinoids and capsinoids of chilli pepper as feed additives in livestock production: Current and future trends.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Review
- Pathway-based cancer transcriptome deciphers a high-resolution intrinsic heterogeneity within bladder cancer classification.Journal of translational medicine · 2025Article
- SLIRP amplifies antiviral signaling via positive feedback regulation and contributes to autoimmune diseases.Cell reports · 2025Article
- Identification of the gene signatures related to NK/T cell communication to evaluate the tumor microenvironment and prognostic outcomes of patients with prostate adenocarcinoma.Frontiers in immunology · 2025Article
- Mitochondrial double-stranded RNA homeostasis depends on cell-cycle progression.Life science alliance · 2024Article
- DAMP sensing and sterile inflammation: intracellular, intercellular and inter-organ pathways.Nature reviews. Immunology · 2024Review
- Mitochondria facilitate neuronal differentiation by metabolising nuclear-encoded RNA.Cell communication and signaling : CCS · 2024Article
- Heterozygous de novo dominant negative mutation of REXO2 results in interferonopathy.Nature communications · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA decay is a key element of mitochondrial RNA metabolism. To date, the only well-documented machinery that plays a role in mtRNA decay in humans is the complex of polynucleotide phosphorylase (PNPase) and SUV3 helicase, forming the degradosome. REXO2, a homolog of prokaryotic oligoribonucleases present in humans both in mitochondria and the cytoplasm, was earlier shown to be crucial for maintaining mitochondrial homeostasis, but its function in mitochondria has not been fully elucidated. In the present study, we created a cellular model that enables the clear dissection of mitochondrial and non-mitochondrial functions of human REXO2. We identified a novel mitochondrial short RNA, referred to as ncH2, that massively accumulated upon REXO2 silencing. ncH2 degradation occurred independently of the mitochondrial degradosome, strongly supporting the hypothesis that ncH2 is a primary substrate of REXO2. We also investigated the global impact of REXO2 depletion on mtRNA, revealing the importance of the protein for maintaining low steady-state levels of mitochondrial antisense transcripts and double-stranded RNA. Our detailed biochemical and structural studies provide evidence of sequence specificity of the REXO2 oligoribonuclease. We postulate that REXO2 plays dual roles in human mitochondria, 'scavenging' nanoRNAs that are produced by the degradosome and clearing short RNAs that are generated by RNA processing.
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