Structure and function of the PWI motif: a novel nucleic acid-binding domain that facilitates pre-mRNA processing

Genes Dev. 2003 Feb 15;17(4):461-75. doi: 10.1101/gad.1060403.


The PWI motif is a highly conserved domain of unknown function in the SRm160 splicing and 3'-end cleavage-stimulatory factor, as well as in several other known or putative pre-mRNA processing components. We show here that the PWI motif is a new type of RNA/DNA-binding domain that has an equal preference for single- and double-stranded nucleic acids. Deletion of the motif prevents SRm160 from binding RNA and stimulating 3'-end cleavage, and its substitution with a heterologous RNA-binding domain restores these functions. The NMR solution structure of the SRm160-PWI motif reveals a novel, four-helix bundle and represents the first example of an alpha-helical fold that can bind single-stranded (ss)RNA. Structure-guided mutagenesis indicates that the same surface is involved in RNA and DNA binding and requires the cooperative action of a highly conserved, adjacent basic region. Thus, the PWI motif is a novel type of nucleic acid-binding domain that likely has multiple important functions in pre-mRNA processing, including SRm160-dependent stimulation of 3'-end formation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Antigens, Nuclear / chemistry*
  • Antigens, Nuclear / genetics
  • Antigens, Nuclear / metabolism*
  • Binding Sites
  • Conserved Sequence
  • HeLa Cells
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Matrix-Associated Proteins / chemistry*
  • Nuclear Matrix-Associated Proteins / genetics
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Nucleic Acids / metabolism
  • Protein Conformation
  • RNA Precursors / metabolism*
  • RNA Processing, Post-Transcriptional
  • RNA Splicing
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Sequence Deletion


  • Antigens, Nuclear
  • Nuclear Matrix-Associated Proteins
  • Nucleic Acids
  • RNA Precursors
  • RNA-Binding Proteins
  • SRRM1 protein, human

Associated data

  • PDB/1MP1