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. Epub 2015 Jul 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Gene Expression Profiling
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Molecular Sequence Data
  • Neutropenia / genetics
  • Neutropenia / pathology
  • Phosphoric Diester Hydrolases / deficiency
  • Phosphoric Diester Hydrolases / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA Splicing
  • RNA Stability*
  • RNA, Small Nuclear / chemistry*
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism*
  • Sequence Analysis, RNA
  • Skin Abnormalities / genetics
  • Skin Abnormalities / pathology


  • RNA, Small Nuclear
  • U6 small nuclear RNA
  • Phosphoric Diester Hydrolases
  • USB1 protein, human

Supplementary concepts

  • Poikiloderma with Neutropenia