Protein splicing of a recombinase intein induced by ssDNA and DNA damage

Genes Dev. 2016 Dec 15;30(24):2663-2668. doi: 10.1101/gad.289280.116. Epub 2016 Dec 28.

Abstract

Inteins (or protein introns) autocatalytically excise themselves through protein splicing. We challenge the long-considered notion that inteins are merely molecular parasites and posit that some inteins evolved to regulate host protein function. Here we show substrate-induced and DNA damage-induced splicing, in which an archaeal recombinase RadA intein splices dramatically faster and more accurately when provided with ssDNA. This unprecedented example of intein splicing stimulation by the substrate of the invaded host protein provides compelling support in favor of inteins acting as pause buttons to arrest protein function until needed; then, an immediate activity switch is triggered, representing a new form of post-translational control.

Keywords: RadA; conditional protein splicing; post-translational regulation.

MeSH terms

  • Archaeal Proteins / genetics*
  • Archaeal Proteins / metabolism
  • DNA Damage / genetics*
  • DNA, Single-Stranded / metabolism*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Escherichia coli / genetics
  • Gene Expression Regulation / genetics
  • Inteins / genetics*
  • Models, Biological
  • Mutation
  • Protein Binding
  • Protein Processing, Post-Translational
  • Protein Splicing / genetics*

Substances

  • Archaeal Proteins
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • RadA protein, archaeal