The PWI domain, named after a highly conserved PWI tri-peptide located within its N-terminal region, is a ~80 amino acid module, which is found either at the N terminus or at the C terminus of eukaryotic proteins involved in pre-mRNA processing [ (PUBMED:10322432) ]. It is generally found in association with other domains such as RRM and RS. The PWI domain is a RNA/DNA-binding domain that has an equal preference for single- and double-stranded nucleic acids and is likely to have multiple important functions in pre-mRNA processing [ (PUBMED:12600940) ]. Proteins containing this domain include the SR-related nuclear matrix protein of 160kDa (SRm160) splicing and 3'-end cleavage-stimulatory factor, and the mammalian splicing factor PRP3.
The PWI domain is a soluble, globular and independently folded domain which consists of a four-helix bundle, with structured N- and C-terminal elements [ (PUBMED:12600940) ].
Structure and function of the PWI motif: a novel nucleic acid-binding domain that facilitates pre-mRNA processing.
Genes Dev. 2003; 17: 461-75
Display 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.
