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

Beneventi, Giulia LU ; Munita, Roberto LU ; Cao Thi Ngoc, Phuong LU ; Madej, Magdalena LU ; Ciesla, Maciej LU ; Muthukumar, Sowndarya LU ; Krogh, Nicolai ; Nielsen, Henrik ; Swaminathan, Vinay LU and Bellodi, Cristian LU (2021) In NAR Cancer 3(3).
Abstract
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 sur- vival, motility and anchorage-independent growth. In sum,... (More)
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 sur- vival, motility and anchorage-independent growth. In sum, these findings highlight an unanticipated role for SCARNA15 and Ψ in directing cancer-associated splicing programs. (Less)
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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
NAR Cancer
volume
3
issue
3
pages
14 pages
publisher
Oxford University Press
external identifiers
  • pmid:34316713
  • scopus:85119260161
ISSN
2632-8674
DOI
10.1093/narcan/zcab026
language
English
LU publication?
yes
id
e572074e-e847-40ac-a067-970aba46c7b5
date added to LUP
2021-10-10 18:53:57
date last changed
2022-12-07 04:06:34
@article{e572074e-e847-40ac-a067-970aba46c7b5,
  abstract     = {{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 sur- vival, motility and anchorage-independent growth. In sum, these findings highlight an unanticipated role for SCARNA15 and Ψ in directing cancer-associated splicing programs.}},
  author       = {{Beneventi, Giulia and Munita, Roberto and Cao Thi Ngoc, Phuong and Madej, Magdalena and Ciesla, Maciej and Muthukumar, Sowndarya and Krogh, Nicolai and Nielsen, Henrik and Swaminathan, Vinay and Bellodi, Cristian}},
  issn         = {{2632-8674}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{3}},
  publisher    = {{Oxford University Press}},
  series       = {{NAR Cancer}},
  title        = {{The small Cajal body-specific RNA 15 (SCARNA15) directs p53 and redox homeostasis via selective splicing in cancer cells}},
  url          = {{http://dx.doi.org/10.1093/narcan/zcab026}},
  doi          = {{10.1093/narcan/zcab026}},
  volume       = {{3}},
  year         = {{2021}},
}