DEF-3(g16/NY-LU-12), an RNA binding protein from the 3p21.3 homozygous deletion region in SCLC

DEF-3(g16/NY-LU-12) encodes a novel RNA binding protein isolated by positio nal cloning from an SCLC homozygous deletion region in 3p21.3 and, in paral lel, as a differentially expressed gene during myelopoiesis from FDCPmix-A4 cells, DEF-3(g16/NY-LU-12) is ubiquitously expressed during mouse embryoge nesis and in adult organs while human hematopoietic tissues showed differen tial expression, The mouse and human proteins are highly conserved containi ng two RNA recognition motifs (RRMs) and other domains associated with RNA binding and protein-protein interactions. A database search identified rela ted proteins in human, rat, C. elegans and S, pombe including the 3p21.3 co -deleted gene, LUCA15, Recombinant proteins containing the RRMs of DEF-3(g1 6/NY-LU-12) and LUCA15 specifically bound poly(G) RNA homopolymers in vitro . These RRMs also show similarity to those of the Hu protein family. Since anti-Hu RRM domain antibodies are associated with an anti-tumor effect and paraneoplastic encephalomyelitis, we tested sera from Hu syndrome patients with the RRMs of DEF-3(g16/NY-LU-12) and LUCA15, These were non-reactive. T hus, DEF-3(g16/NY-LU-12) and LUCA15 represent members of a novel family of RNA binding proteins with similar expression patterns and in vitro RNA bind ing characteristics. They are co-deleted in some lung cancers and immunolog ically distinct from the Hu proteins.