ArticleGenome research2015
DIS3 shapes the RNA polymerase II transcriptome in humans by degrading a variety of unwanted transcripts.
Article in Genome research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55 citing papers in PubMed, 96 citations in OpenAlex.
- Ribonuclease DIS3 delays aging and senescence by generating tRNA halves.Nature communications · 2026Article
- DIS3 mutations enhance AID-driven translocations during B-cell activation, promoting transformation to multiple myeloma.Nature communications · 2026Article
- Defining the roles of the Integrator, NEXT, and nuclear exosome complexes in Drosophila oogenesis.Cell reports · 2025Article
- The regulation and function of post-transcriptional RNA splicing.Nature reviews. Genetics · 2025Review
- DIS3L, cytoplasmic exosome catalytic subunit, is essential for development but not cell viability in mice.RNA (New York, N.Y.) · 2025Article
- Functional characterization of human recessive DIS3 variants in premature ovarian insufficiency†.Biology of reproduction · 2025Article
- DNA-directed termination of mammalian RNA polymerase II.Genes & development · 2024Article
- A Comparative Overview of the Role of Human Ribonucleases in Nonsense-Mediated mRNA Decay.Genes · 2024Article
- Article
- DIS3 ribonuclease is essential for spermatogenesis and male fertility in mice.Development (Cambridge, England) · 2024Article
- LINE-1 transcription activates long-range gene expression.Nature genetics · 2024Article
- SnoRNAs: Exploring Their Implication in Human Diseases.International journal of molecular sciences · 2024Review
- Article
- DIS3 Variants are Associated With Primary Ovarian Insufficiency: Importance of Transcription/Translation in Oogenesis.The Journal of clinical endocrinology and metabolism · 2023Observational
- Multiomic analysis of cohesin reveals that ZBTB transcription factors contribute to chromatin interactions.Nucleic acids research · 2023Article
- Review
- Maturation of small nucleolar RNAs: from production to function.RNA biology · 2023Review
- Loss of ribonuclease DIS3 hampers genome integrity in myeloma by disrupting DNA:RNA hybrid metabolism.The EMBO journal · 2022Article
- MPP6 stimulates both RRP6 and DIS3 to degrade a specified subset of MTR4-sensitive substrates in the human nucleus.Nucleic acids research · 2022Article
- Rapid factor depletion highlights intricacies of nucleoplasmic RNA degradation.Nucleic acids research · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human DIS3, the nuclear catalytic subunit of the exosome complex, contains exonucleolytic and endonucleolytic active domains. To identify DIS3 targets genome-wide, we combined comprehensive transcriptomic analyses of engineered HEK293 cells that expressed mutant DIS3, with Photoactivatable Ribonucleoside-Enhanced Cross-Linking and Immunoprecipitation (PAR-CLIP) experiments. In cells expressing DIS3 with both catalytic sites mutated, RNAs originating from unannotated genomic regions increased ∼2.5-fold, covering ∼70% of the genome and allowing for thousands of novel transcripts to be discovered. Previously described pervasive transcription products, such as Promoter Upstream Transcripts (PROMPTs), accumulated robustly upon DIS3 dysfunction, representing a significant fraction of PAR-CLIP reads. We have also detected relatively long putative premature RNA polymerase II termination products of protein-coding genes whose levels in DIS3 mutant cells can exceed the mature mRNAs, indicating that production of such truncated RNA is a common phenomenon. In addition, we found DIS3 to be involved in controlling the formation of paraspeckles, nuclear bodies that are organized around NEAT1 lncRNA, whose short form was overexpressed in cells with mutated DIS3. Moreover, the DIS3 mutations resulted in misregulation of expression of ∼50% of transcribed protein-coding genes, probably as a secondary effect of accumulation of various noncoding RNA species. Finally, cells expressing mutant DIS3 accumulated snoRNA precursors, which correlated with a strong PAR-CLIP signal, indicating that DIS3 is the main snoRNA-processing enzyme. EXOSC10 (RRP6) instead controls the levels of the mature snoRNAs. Overall, we show that DIS3 has a major nucleoplasmic function in shaping the human RNA polymerase II transcriptome.
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