Characterization of the mammalian RNA exonuclease 5/NEF-sp as a testis-specific nuclear 3' → 5' exoribonuclease

RNA. 2017 Sep;23(9):1385-1392. doi: 10.1261/rna.060723.117. Epub 2017 May 24.


Ribonucleases catalyze maturation of functional RNAs or mediate degradation of cellular transcripts, activities that are critical for gene expression control. Here we identify a previously uncharacterized mammalian nuclease family member NEF-sp (RNA exonuclease 5 [REXO5] or LOC81691) as a testis-specific factor. Recombinant human NEF-sp demonstrates a divalent metal ion-dependent 3' → 5' exoribonuclease activity. This activity is specific to single-stranded RNA substrates and is independent of their length. The presence of a 2'-O-methyl modification at the 3' end of the RNA substrate is inhibitory. Ectopically expressed NEF-sp localizes to the nucleolar/nuclear compartment in mammalian cell cultures and this is dependent on an amino-terminal nuclear localization signal. Finally, mice lacking NEF-sp are viable and display normal fertility, likely indicating overlapping functions with other nucleases. Taken together, our study provides the first biochemical and genetic exploration of the role of the NEF-sp exoribonuclease in the mammalian genome.

Keywords: 2610020H08Rik; LOC81691; NEF-sp; Q96IC2; REXO5; REXON; RNA exonuclease 5.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cations, Divalent / chemistry
  • Cations, Divalent / metabolism
  • Cell Line
  • Cell Nucleus
  • Exoribonucleases / chemistry
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism*
  • Humans
  • Male
  • Mammals
  • Mice
  • Mice, Knockout
  • Mutation
  • Organ Specificity
  • RNA / metabolism*
  • Recombinant Proteins
  • Substrate Specificity
  • Testis / metabolism*


  • Cations, Divalent
  • Recombinant Proteins
  • RNA
  • Exoribonucleases