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Haplotype-specific sequence encoding the protein kinase, interferon-inducible double-stranded RNA-dependent activator
1Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Japan.
Abstract:
The protein kinase, interferon-inducible double-stranded (ds)RNA-dependent activator (PRKRA) is a dsRNA-binding protein which activates a protein kinase participating in the antiviral activity of interferon. Our previous studies indicated that the nucleotide sequence encoding PRKRA, which appeared to be an intronless gene, was present in PAC HS265J14 containing the human leukocyte 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 for HLA genes. Results indicated that the presence of PRKRA in the DR subregion was dependent on the DR53 group. Consistently, fluorescence in situ hybridization profiles with PRKRA as a probe showed that the hybridization signal on Chromosome (Chr) 6p21.3 was seen only in the samples carrying the DR haplotypes that belonged to the DR53 group. Interestingly, another hybridization 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 draft-sequence, RP11-65L3 (GenBank accession number AC009948), which is located between D2S335 and D2S2257. Together, the data presented here indicate that the PRKRA gene in the DR subregion is a processed pseudogene (PRKRApsi), which could have been generated only on the DR53 common ancestor's genome, and that the master copy of PRKRApsi is most probably present on Chr 2q31.2-q32.1.
Insights
The protein kinase, interferon-inducible double-stranded RNA-dependent activator (PRKRA) gene in the HLA-DR subregion is a processed pseudogene, likely originating from a functional gene on Chromosome 2. This pseudogene
Area of Science:
- Genetics
- Immunology
- Molecular Biology
Background:
- The protein kinase, interferon-inducible double-stranded (ds)RNA-dependent activator (PRKRA) is a dsRNA-binding protein crucial for interferon's antiviral activity.
- Previous studies suggested an intronless PRKRA gene sequence within the human leukocyte antigen (HLA) DR subregion.
Purpose of the Study:
- To investigate and characterize the PRKRA gene's location and nature within the human genome.
- To determine the origin and relationship of the PRKRA sequence in the HLA DR subregion.
Main Methods:
- Southern blotting and polymerase chain reaction (PCR) using homozygous typing cell lines for HLA genes.
- Fluorescence in situ hybridization (FISH) with PRKRA as a probe.
- Sequence-database homology search.
Main Results:
- The PRKRA sequence in the DR subregion was found to be dependent on the DR53 group.
- FISH analysis revealed PRKRA signals on Chromosome (Chr) 6p21.3 (DR53-dependent) and Chr 2q31.2-q32.1 (consistently detected).
- Homology searches indicated an intron-containing PRKRA gene on Chr 2, suggesting the Chr 6 sequence is a processed pseudogene (PRKRApsi).
Conclusions:
- The PRKRA gene found in the HLA DR subregion is a processed pseudogene (PRKRApsi).
- This pseudogene likely originated from a functional PRKRA gene on Chr 2q31.2-q32.1.
- The generation of PRKRApsi appears linked to the DR53 group's common ancestor.