The small Cajal body-specific RNA 15 (SCARNA15) directs p53 and redox homeostasis via selective splicing in cancer cells
| Autor: | Sowndarya Muthukumar, Cristian Bellodi, Roberto Munita, Magdalena Madej, Vinay Swaminathan, Phuong Cao Thi Ngoc, Maciej Cieśla, Henrik Nielsen, Giulia Beneventi, Nicolai Krogh |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
AcademicSubjects/SCI01140
0303 health sciences AcademicSubjects/SCI01060 Alternative splicing AcademicSubjects/SCI00030 RNA General Medicine Standard Article Biology AcademicSubjects/SCI01180 Chromatin Cell biology 03 medical and health sciences 0302 clinical medicine 030220 oncology & carcinogenesis RNA splicing Cancer cell U2 spliceosomal RNA AcademicSubjects/SCI00980 ATRX 030304 developmental biology Small Cajal body specific RNA 15 |
| Zdroj: | Beneventi, G, Munita, R, Cao Thi Ngoc, P, Madej, M, Cieśla, M, Muthukumar, S, Krogh, N, Nielsen, H, Swaminathan, V & Bellodi, C 2021, ' The small Cajal body-specific RNA 15 (SCARNA15) directs p53 and redox homeostasis via selective splicing in cancer cells ', NAR Cancer, vol. 3, no. 3, zcab026 . https://doi.org/10.1093/narcan/zcab026 NAR Cancer |
| DOI: | 10.1093/narcan/zcab026 |
| Popis: | 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. Graphical Abstract Graphical AbstractOverexpression of SCARNA15 is associated with MYC alterations in multiple cancer subtypes. Mechanistically, SCARNA15-guided U2 pseudouridylation (Ψ39) directs distinct alternative splicing events to impact cancer cell anchorage independence, motility and survival upon oxidative stress. |
| Databáze: | OpenAIRE |
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