Chromosomal instability by mutations in the novel minor spliceosome component CENATAC

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de Wolf , B , Oghabian , A , Akinyi , M , Hanks , S , Tromer , E C , van Hooff , J J E , van Voorthuijsen , L , van Rooijen , L E , Verbeeren , J , Uijttewaal , E C H , Baltissen , M P A , Yost , S , Piloquet , P , Vermeulen , M , Snel , B , Isidor , B , Rahman , N , Frilander , M J & Kops , G J P L 2021 , ' Chromosomal instability by mutations in the novel minor spliceosome component CENATAC ' , EMBO Journal , vol. 40 , no. 14 , 106536 . https://doi.org/10.15252/embj.2020106536

Title: Chromosomal instability by mutations in the novel minor spliceosome component CENATAC
Author: de Wolf, Bas; Oghabian, Ali; Akinyi, Maureen; Hanks, Sandra; Tromer, Eelco C.; van Hooff, Jolien J. E.; van Voorthuijsen, Lisa; van Rooijen, Laura E.; Verbeeren, Jens; Uijttewaal, Esther C. H.; Baltissen, Marijke P. A.; Yost, Shawn; Piloquet, Philippe; Vermeulen, Michiel; Snel, Berend; Isidor, Bertrand; Rahman, Nazneen; Frilander, Mikko J.; Kops, Geert J. P. L.
Other contributor: University of Helsinki, CAMM - Research Program for Clinical and Molecular Metabolism
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology


Date: 2021-07-15
Language: eng
Number of pages: 18
Belongs to series: EMBO Journal
ISSN: 0261-4189
DOI: https://doi.org/10.15252/embj.2020106536
URI: http://hdl.handle.net/10138/333324
Abstract: Aneuploidy is the leading cause of miscarriage and congenital birth defects, and a hallmark of cancer. Despite this strong association with human disease, the genetic causes of aneuploidy remain largely unknown. Through exome sequencing of patients with constitutional mosaic aneuploidy, we identified biallelic truncating mutations in CENATAC (CCDC84). We show that CENATAC is a novel component of the minor (U12-dependent) spliceosome that promotes splicing of a specific, rare minor intron subtype. This subtype is characterized by AT-AN splice sites and relatively high basal levels of intron retention. CENATAC depletion or expression of disease mutants resulted in excessive retention of AT-AN minor introns in similar to 100 genes enriched for nucleocytoplasmic transport and cell cycle regulators, and caused chromosome segregation errors. Our findings reveal selectivity in minor intron splicing and suggest a link between minor spliceosome defects and constitutional aneuploidy in humans.
Subject: aneuploidy
CCDC84
CENATAC
minor spliceosome
MOSAIC VARIEGATED ANEUPLOIDY
U12-TYPE INTRONS
HUMAN INTERACTOME
U11 SNRNP
PROTEIN
GENE
CHECKPOINT
RNU4ATAC
IDENTIFICATION
CEP57
1184 Genetics, developmental biology, physiology
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