M1204, a novel 2 ',5 ' oligoadenylate synthetase with a ubiquitin-like extension, is induced during maturation of murine dendritic cells

A novel molecule expressed by spleen dendritic cells (DC) was isolated usin g a subtractive hybridization approach, The full-length M1204 clone has 306 3 bp, with 1415 bp spanning a single open reading frame, coding for a prote in of a predicted size of about 50 kDa, This sequence has strong homology t o 2', 5' oligoadenylate synthetase and contains a ubiquitin-like domain. In Northern blot analyses the mRNA is strongly expressed in spleen DC, wherea s, in bone marrow-derived DC, the amount of mRNA increases during the matur ation process. None of the other leukocytes nor several hemopoietic cell li nes tested express this mRNA, but clear expression occurs in many organs, t he highest levels being in thymus, lung, and hone marrow. In situ hybridiza tion, combined with immunocytochemical staining of tissue sections of lung and spleen, shows colocalization of M1204 vwith the 2Al and NLDC DC markers . In Western blot experiments, an antiserum raised against the recombinant M1204 recognizes a single band in bone marrow-derived DC and in the lung. T he expressed oligoadenylate synthetase domain is active in synthesizing 2', 5' diadenylate, which by itself may inhibit viral protein synthesis and may also function as a substrate for 2',5' oligaadenylate synthetase, Since th e oligoadenylate/RNase L system provides early protection against virus inf ection, we hypothesize that M1204 prevents virus-induced cell death in DC.