The small Cajal body-specific RNA 15 (SCARNA15) directs p53 and redox homeostasis via selective splicing in cancer cells.

Autor:	Beneventi G; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, 22184, Lund, Sweden., Munita R; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, 22184, Lund, Sweden., Cao Thi Ngoc P; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, 22184, Lund, Sweden., Madej M; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, 22184, Lund, Sweden., Cieśla M; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, 22184, Lund, Sweden., Muthukumar S; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, 22184, Lund, Sweden., Krogh N; Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, 2200, Copenhagen, Denmark., Nielsen H; Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, 2200, Copenhagen, Denmark., Swaminathan V; Division of Oncology, Department of Clinical Sciences, Lund University, 22184, Lund, Sweden., Bellodi C; Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, 22184, Lund, Sweden.
Jazyk:	angličtina
Zdroj:	NAR cancer [NAR Cancer] 2021 Jul 09; Vol. 3 (3), pp. zcab026. Date of Electronic Publication: 2021 Jul 09 (Print Publication: 2021).
DOI:	10.1093/narcan/zcab026
Abstrakt:	Small Cajal body-specific RNAs (scaRNAs) guide post-transcriptional modification of spliceosomal RNA and, while commonly altered in cancer, have poorly defined roles in tumorigenesis. Here, we uncover that SCARNA15 directs alternative splicing (AS) and stress adaptation in cancer cells. Specifically, we find that SCARNA15 guides critical pseudouridylation (Ψ) of U2 spliceosomal RNA to fine-tune AS of distinct transcripts enriched for chromatin and transcriptional regulators in malignant cells. This critically impacts the expression and function of the key tumor suppressors ATRX and p53. Significantly, SCARNA15 loss impairs p53-mediated redox homeostasis and hampers cancer cell survival, motility and anchorage-independent growth. In sum, these findings highlight an unanticipated role for SCARNA15 and Ψ in directing cancer-associated splicing programs. (© The Author(s) 2021. Published by Oxford University Press on behalf of NAR Cancer.)
Databáze:	MEDLINE
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