Tao et al. uncover a DIS3-mediated circRNA degradation pathway, which occurs in the cytoplasm and is independent of the RNA exosome complex. DIS3 recognizes circRNAs containing U-rich motifs and requires its endonucleolytic activity for degradation.…

CircRNAs are generated during splicing, but their specific degradation pathways are poorly understood. Latini et al. identify and biochemically characterize the exo- and endoribonuclease DIS3 as a candidate for cytoplasmic circRNA degradation. DIS3 uses its catalytic PIN domain to cleave circRNAs and functions in the cytoplasm independently of the exosome.

Tao et al. uncover a DIS3-mediated circRNA degradation pathway, which occurs in the cytoplasm and is independent of the RNA exosome complex. DIS3 recognizes circRNAs containing U-rich motifs and requires its endonucleolytic activity for degradation. Synthetic RNA circles with U-rich motifs show altered degradation rates in vitro and in cells.

Cellular & Molecular Immunology - DIS3 licenses B cells for plasma cell differentiation in humans

Features of circular RNAs (circRNAs) produced by back-splicing of eukaryotic exon(s) make them resistant to degradation by linear RNA decay machinerie…

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Enervald et al. show that DIS3, one of the catalytic subunits of the human RNA exosome, facilitates the resolution of stalled RNAPII transcription complexes by engaging in the degradation of the 3′ end of backtracked RNA. This activity of DIS3 is necessary for efficient transcription elongation.

Author summary R-loops are three-stranded structures formed by a DNA-RNA hybrid and the displaced ssDNA. The accumulation of R-loops damages the genome, highlighting the need for their tight regulatio...

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Transfer RNA (tRNA) halves (tRHs) are generated via the cleavage of tRNAs, but their roles in aging and longevity remain poorly understood. Here, we demonstrate a direct role of tRHs in aging in metazoans. Through a genetic screen using Caenorhabditis elegans, we identify DIS-3/DIS3 as a ribonuclease that catalyzes tRH generation, including 5′-tRH-Gln and 5′-tRH-Asp, from tRNAs. Among them, 5′-tRH-Gln is essential for longevity conferred by various interventions, including dietary restriction. Generation of 5′-tRH-Gln reduces translation via ribosomal protein binding and upregulates the SKN-1/NRF transcription factor responsible for lifespan extension. We further show that mammalian DIS3 contributes to tRH generation and delays cellular senescence through translation downregulation by another tRH, 5′-tRH-Cys. Overall, our data demonstrate that DIS-3/DIS3 is an evolutionarily conserved tRH-generating ribonuclease that counteracts organismal and cellular aging. Direct roles of tRNA halve

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Cellular & Molecular Immunology - DIS3 licenses B cells for plasma cell differentiation in humans

CircRNAs are generated during splicing, but their specific degradation pathways are poorly understood. Latini et al. identify and biochemically characterize the exo- and endoribonuclease DIS3 as a can...

Direct roles of tRNA halves in aging are unclear. Here, the authors identify DIS-3/DIS3 as a conserved ribonuclease that generates tRNA halves, which delay aging and senescence by binding ribosome and...

Immunoglobulin class switch recombination requires the activity of the RNA-degrading enzyme DIS3, and mutations affecting DIS3 exoribonucleolytic activity are common in multiple myeloma, implying that these dominant variants could be causal to B lymphoid tumorigenesis. Here the authors generate knock-in mice carrying the human DIS3 G766R mutation, which leads to plasmacytoid tumorigenesis via impairing the precision of AID-targeting.

YouTube video by Tsuruta Kamo - Topic

Mammalian development is precisely controlled by cell differentiation. Discovery of new regulators and investigating their crosstalk provide insights into genetic networks defining pre-implantation de...