The Mpn1 RNA exonuclease: cellular functions and implication in disease.

Recent studies from independent laboratories have decisively disclosed the identity of the long-sought 3-5' RNA exonuclease that trims posttranscriptionally the oligouridine tail of U6, which is the small catalytic non-coding RNA promoting premRNA splicing within the spliceosome. This exonuclease, dubbed Mpn1 or Usb1, is a highly conserved enzyme that specifically removes uridines from the 3' end of U6, and directly generates terminal 2',3' cyclic phosphate groups. Mutations in the human gene encoding hMpn1 have been reported in patients diagnosed with the rare genodermatosis Clericuzio-type poikiloderma with neutropenia (PN). Mpn1-associated functions in U6 small nuclear RNA posttranscriptional regulation suggest the existence of sophisticated cellular pathways involved in surveillance and stabilization of U6. In this light, PN pathology might turn out to be a consequence of disturbed quality control of RNAs involved in crucial biological events.