2. Academic Validation
  3. Human Mpn1 promotes post-transcriptional processing and stability of U6atac

Human Mpn1 promotes post-transcriptional processing and stability of U6atac

  • FEBS Lett. 2015 Aug 19;589(18):2417-23. doi: 10.1016/j.febslet.2015.06.046.
Vadim Shchepachev 1,  Harry Wischnewski 1,  Charlotte Soneson 2,  Andreas W Arnold 3,  Claus M Azzalin 4
Affiliations

Affiliations

  • 1 Institute of Biochemistry (IBC), Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich CH-8093, Switzerland.
  • 2 Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne CH-1015, Switzerland.
  • 3 Dermatologische Universitätsklinik, Universitätsspital Basel, Basel CH-4031, Switzerland.
  • 4 Institute of Biochemistry (IBC), Eidgenössische Technische Hochschule Zürich (ETHZ), Zürich CH-8093, Switzerland. Electronic address: [email protected].
PMID: 26213367 DOI: 10.1016/j.febslet.2015.06.046
Abstract

Mpn1 is an exoribonuclease that modifies the spliceosomal small nuclear RNA (snRNA) U6 by trimming its oligouridine tail and introducing a cyclic phosphate group (>p). Mpn1 deficiency induces U6 3' end misprocessing, accelerated U6 decay and pre-mRNA splicing defects. Mutations in the human MPN1 gene are associated with the genodermatosis Clericuzio-type poikiloderma with neutropenia (PN). Here we present the deep sequencing of the >p-containing transcriptomes of mpn1Δ fission yeast and PN cells. While in yeast U6 seems to be the only substrate of Mpn1, human Mpn1 also processes U6atac snRNA. PN cells bear unstable U6atac species with aberrantly long and oligoadenylated 3' ends. Our data corroborate the link between Mpn1 and snRNA stability suggesting that PN could derive from pre-mRNA splicing aberrations.

Keywords

Mpn1; Poikiloderma with neutropenia; Pre-mRNA splicing; U6atac.

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