Rothmund-Thomson syndrome responsible gene, RECQL4: Genomic structure and products

RECQL4 is the fourth gene identified as a member of the human DNA helicase RecQ gene family including the genes for Werner syndrome (WRN) and Bloom syndrome, both of which are characterized by genomic instability. Recently, RECQL4 was identified as the gene responsible for some cases of Rothmund-Thomson syndrome (RTS), a rare autosomal recessive genetic disorder that shows chromosomal instability, premature aging, and a high risk of mesenchymal tumors. In this study, we show the genomic organization of the RECQL4 gene, including the exon-intron boundaries, the transcription initiation sites, and the potential promoter sequences, which facilitates further mutation analysis of the RECQL4 gene and studies to elucidate the pathogenesis behind RTS. The RECQL4 gene is in a small genome of 6.5 kb and consists of 21 exons. In the 5' upstream region, one Sp1 site and several AP 2 sites exist near the capping site, suggesting that the expression of RECQL4 is regulated by a housekeeping-type promoter similar to WRN. By comparative Northern blot analysis, we show that the RECQL4 transcripts are severely down-regulated in the cells from RTS patients, similar to our previous observation for WRN transcripts in cells from Werner patients. Immunocytochemical analysis indicated that the RECQL4 protein expressed in HeLa cells is in the nucleus and appears to be localized mainly in the nucleoplasm similar to WRN helicase.