DIS3L, cytoplasmic exosome catalytic subunit, is essential for development but not cell viability in mice.

Among numerous enzymes involved in RNA decay, processive exoribonucleases are the most prominent group responsible for the degradation of entire RNA molecules. The role of mammalian cytoplasmic 3'-5' exonuclease DIS3L at the organismal level remained unknown. Herein, we established knock-in and knockout (KO) mouse models to study DIS3L functions in mice. DIS3L in mice is indeed a subunit of the cytoplasmic exosome complex, the disruption of which leads to severe embryo degeneration and death in mice soon after implantation. These changes could not be prevented by supplementing extraembryonic tissue with functional DIS3L through the construction of chimeric embryos. Preimplantation <i>Dis3l</i> <sup>-/-</sup> embryos were unaffected in their morphology and ability to produce functional embryonic stem (ES) cells, showing that DIS3L is not essential for cell viability. There were also no major changes at the transcriptome level for both ES cells and blastocysts, as revealed by RNA-seq experiments. Notably, however, <i>Dis3l</i> KO led to inhibition of global protein synthesis. These results point to the essential role of DIS3L in mRNA metabolism, which is crucial for proper protein synthesis during embryo development.

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Publication Details

Journal
RNA
Published
2025-02-07
DOI
https://doi.org/10.1261/rna.080350.124
Citations
2
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
1.61

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article

DIS3L, cytoplasmic exosome catalytic subunit, is essential for development but not cell viability in mice.

Olga Gewartowska, Tomasz M. Kuliński, Dominik Cysewski, Ewa Borsuk et al.
2 citations
RNA
Extracellular vesicles in disease
1.61
article

DIS3L, cytoplasmic exosome catalytic subunit, is essential for development but not cell viability in mice.

Olga Gewartowska, Tomasz M. Kuliński, Dominik Cysewski, Ewa Borsuk, Dorota Adamska, Seweryn Mroczek, Areta M. Czerwińska, Marcin Szpila, Anna Hojka-Osińska, Jakub Gruchota, Michał Brouze, Andrzej Dziembowski, Wiktor Antczak
article en
2 citations

Abstract

Among numerous enzymes involved in RNA decay, processive exoribonucleases are the most prominent group responsible for the degradation of entire RNA molecules. The role of mammalian cytoplasmic 3'-5' exonuclease DIS3L at the organismal level remained unknown. Herein, we established knock-in and knockout (KO) mouse models to study DIS3L functions in mice. DIS3L in mice is indeed a subunit of the cytoplasmic exosome complex, the disruption of which leads to severe embryo degeneration and death in mice soon after implantation. These changes could not be prevented by supplementing extraembryonic tissue with functional DIS3L through the construction of chimeric embryos. Preimplantation <i>Dis3l</i> <sup>-/-</sup> embryos were unaffected in their morphology and ability to produce functional embryonic stem (ES) cells, showing that DIS3L is not essential for cell viability. There were also no major changes at the transcriptome level for both ES cells and blastocysts, as revealed by RNA-seq experiments. Notably, however, <i>Dis3l</i> KO led to inhibition of global protein synthesis. These results point to the essential role of DIS3L in mRNA metabolism, which is crucial for proper protein synthesis during embryo development.

RNAVol. 31(5)
Medical University of Białystok (PL), Department of Embryology (US), International Institute of Molecular and Cell Biology (PL), Institute of Biochemistry and Biophysics, Polish Academy of Sciences (PL), AM Technologies (Poland) (PL), University of Warsaw (PL)
European Commission, Międzynarodowy Instytut Biologii Molekularnej i Komórkowej w Warszawie, HORIZON EUROPE Framework Programme, Institute of Molecular and Cell Biology
Openalex Percentile: Top 19%
Extracellular vesicles in disease
1.61
DOIOpen Access PDFOpenAlex
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