ArticleNucleic acids research2025
The 3'-5' exoribonuclease ISG20L2 contributes to 3' terminus maturation of 18S and 28S ribosomal RNAs.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Functional impact of the eIF6 N106S mutation on ribosome biogenesis in wild type and Shwachman-Diamond syndrome cells.Molecular medicine (Cambridge, Mass.) · 2026Article
- Multi-omics and experimental validation reveal ISG20L2 as a potential pro-oncogenic regulator in gastric cancer.Frontiers in oncology · 2026Article
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10 authors.
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Abstract
Ribosome biogenesis is a nodal process in cell growth and proliferation, and its dysfunction is associated with human congenital diseases and tumorigenesis. Despite extensive mechanistic characterization, several processing steps of human pre-ribosomal RNAs (rRNAs) remain elusive. The 47S primary transcript contains three out of four rRNAs flanked by external (5'ETS, 3'ETS) and internal (ITS1, ITS2) transcribed spacers. The molecular processes leading to the removal of the 3' external transcribed spacer (ETS), one of the earliest maturation steps, is not fully understood. Combining loss-of-function experiments and 3'-RACE high-throughput sequencing, we showed that the vertebrate-specific 3'-5' exoribonuclease ISG20L2, a DEDDh RNase T superfamily member, is critical for efficient removal of the 3'ETS and formation of large ribosomal subunits. ISG20L2 inactivation led to accumulation of various forms of 3'-extended pre-rRNAs and disorganized peripheral dense fibrillar component, a sub-nucleolar compartment recently linked to 3'ETS processing. The function of ISG20L2 also extends to the trimming of ITS1 after endonucleolytic cleavage at site 2 and points to its contribution to the 3' processing of U8 small nucleolar RNA precursor. Altogether, the present work uncovers the landscape of these processing steps at nucleotide resolution, and reveals the function of ISG20L2 with respect to the maturation of 18S and 28S 3' ends.
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