Perlman syndrome nuclease DIS3L2 controls cytoplasmic non-coding RNAs and provides surveillance pathway for maturing snRNAs.
Nucleic Acids Res
; 44(21): 10437-10453, 2016 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-27431325
ABSTRACT
The exosome-independent exoribonuclease DIS3L2 is mutated in Perlman syndrome. Here, we used extensive global transcriptomic and targeted biochemical analyses to identify novel DIS3L2 substrates in human cells. We show that DIS3L2 regulates pol II transcripts, comprising selected canonical and histone-coding mRNAs, and a novel FTL_short RNA from the ferritin mRNA 5' UTR. Importantly, DIS3L2 contributes to surveillance of maturing snRNAs during their cytoplasmic processing. Among pol III transcripts, DIS3L2 particularly targets vault and Y RNAs and an Alu-like element BC200 RNA, but not Alu repeats, which are removed by exosome-associated DIS3. Using 3' RACE-Seq, we demonstrate that all novel DIS3L2 substrates are uridylated in vivo by TUT4/TUT7 poly(U) polymerases. Uridylation-dependent DIS3L2-mediated decay can be recapitulated in vitro, thus reinforcing the tight cooperation between DIS3L2 and TUTases. Together these results indicate that catalytically inactive DIS3L2, characteristic of Perlman syndrome, can lead to deregulation of its target RNAs to disturb transcriptome homeostasis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
RNA Nuclear Pequeno
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Processamento Pós-Transcricional do RNA
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RNA não Traduzido
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Exorribonucleases
Tipo de estudo:
Prognostic_studies
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Screening_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article