Characterization of the human DNAS1L2 gene and the molecular mechanism for its transcriptional activation induced by inflammatory cytokines.

DNAS1L2, a member of the DNase I-like endonuclease family, is the only divalent cation-dependent acid DNase so far identified in mammals. The presence of a proline-rich domain (PRD) is its unique feature among family members. We found that a novel transcript encoding a short product, DNAS1L2-S, is expressed in peripheral blood leukocytes. Although DNAS1L2-S lacks the PRD, its enzymatic properties are apparently the same as those of the previously identified long form, DNAS1L2-L. Sequence analysis reveals that DNAS1L2 consists of seven exons. The exon/intron boundaries agree with the GT/AG rule with one exception: GC replaces GT at the 5' splice site in the sixth intron. TNF-alpha and IL-1beta are found to be potent inducers of DNAS1L2 expression in keratinocytes. They induce DNAS1L2 activation via the NF-kappaB pathway, and an NF-kappaB binding site located within the 5' flanking region is identified as the cis-responsive element.