Haplotype-specific sequence encoding the protein kinase, interferon-inducible double-stranded RNA-dependent activator in the human leukocyte antigen class II region

The protein kinase, interferon-inducible double-stranded (ds)RNA-dependent activator (PRKRA) is a dsRNA-binding protein which activates a protein kina se participating in the antiviral activity of interferon. Our previous stud ies indicated that the nucleotide sequence encoding PRKRA, which appeared t o be an intronless gene, was present in PAC HS265J14 containing the human l eukocyte antigen (HLA) DR subregion. In this study, we further investigated and characterized the PRKRA gene on the human genome by means of Southern blotting and polymerase chain reaction with homozygous typing cell lines fo r HLA genes. Results indicated that the presence of PRKRA in the DR subregi on was dependent on the DR53 group. Consistently, fluorescence in situ hybr idization profiles with PRKRA as a probe showed that the hybridization sign al on Chromosome (Chr) 6p21.3 was seen only in the samples carrying the DR haplotypes that belonged to the DR53 group. Interestingly, another hybridiz ation signal, which was mapped on Chr 2q31.2-q32.1, was always detected in the samples examined, i.e., even in the samples negative for the DR53 group . The outcome of a sequence-database homology search further indicated that the PRKRA gene with introns appeared to be present in a recently opened dr aft-sequence, RP11-65L3 (GenBank accession number AC009938), which is locat ed between D2S335 and D2S2257. Together, the data presented here indicate t hat the PRKRA gene ill the DR subregion is a processed pseudogene (PRKRA Ps i), which could have been generated only on the DR53 common ancestor's geno me, and that the master copy of PRKRA Psi is most probably present on Chr 2 q31.2-q32.1.