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Genes Dev. 2003 Feb 15;17(4):461-75.

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

Author information

  • 1Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada M5G 2M9.

Abstract

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.

PMID:
12600940
[PubMed - indexed for MEDLINE]
PMCID:
PMC196000
Free PMC Article

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