A specific isoform of hnRNP D interacts with DNA in the LR1 heterodimer: Canonical RNA binding motifs in a sequence-specific duplex DNA binding protein

Abstract

The B cell-specific, sequence-specific duplex DNA-binding protein LR1 is a transcriptional activator and may also function in heavy chain class switch recombination. LR1 is composed of two polypeptides, a 106-kDa subunit that is nucleolin, and a 45-kDa subunit that we now show to be a specific isoform of hnRNP D. hnRNP D and nucleolin both contain canonical RNA binding domains (RBDs also called RRMs) and Arg-Gly-Gly (RGG) motifs. Although these motifs are not commonly associated with sequence-specific recognition of duplex DNA, nonetheless LR1 binds duplex DNA with high affinity (K(D) = 1.8 nM) and clear sequence specificity. Two RBD-RGG proteins can therefore combine to produce a sequence-specific duplex DNA-binding protein.