THE BAT1 GENE IN THE MHC ENCODES AN EVOLUTIONARILY CONSERVED PUTATIVENUCLEAR-RNA HELICASE OF THE DEAD FAMILY

The BAT1 gene has previously been identified about 30 kb upstream from the tumor necrosis factor (TNF) locus and close to a NF kappa b-relat ed gene of the nuclear factor family in the major histocompatibility c omplex (MHC) of human, mouse, and pig. We now show that the BAT1 trans lation product is the homolog of the rat p47 nuclear protein, the WM6 Drosophila gene product, and probably also Ce08102 of Caenorhabditis e legans, all members of the DEAD protein family of ATP-dependent RNA he licases. This family has more than 40 members, including the eukaryoti c translation initiation factor-4A (eIF-4A), the human nuclear protein p68, and the Drosophila oocyte polar granule component vasa. BAT1 spa ns about 10 kb, is split into 10 exons of varying length, and encodes a protein of 428 amino acids (similar to 48 kDa). Human and pig BAT1 c DNAs display 95.6% identity in the coding region and 80% identity in t he 5' and 3' noncoding regions. Several repeat sequences of different types were identified in introns of the porcine BAT1 gene. Three diffe rent mRNAs, 4.1, 1.7, and 0.9 kb, respectively, were detected in all t issues analyzed upon hybridization with porcine BAT1 cDNA Transfection and expression of human BAT1 cDNA after tagging with a heterologous a ntibody recognition epitope revealed a nuclear localization of the hyb rid protein. An MspI RFLP was detected in an SLA class I typed family, confirming the localization of the BAT1 gene in the porcine MHC. BAT1 thus encodes a putative nuclear ATP-dependent RNA helicase and is lik ely to have an indispensable function. (C) 1995 Academic Press, Inc.