PROTOONCOGENE-SNO EXPRESSION, ALTERNATIVE ISOFORMS AND IMMEDIATE-EARLY SERUM RESPONSE

The mouse Sno gene, a Ski proto-oncogene homolog, expresses two isofor ms, SnoN and SnoN2 (also called sno-dE3), which differ from each other in a location downstream from the site of alternative splicing previo usly described in the human SNO gene, SnoN2 is missing a 138 nt coding segment present in mouse SnoN and human SNON. We have cloned and sequ enced the human ortholog of mouse SnoN2, the existence of which was pr edicted from conservation of the alternative splice donor site that pr oduces the SnoN2 isoform, Mouse SnoN2 and SnoN are expressed throughou t embryonic development, in neonatal muscle and in many adult tissues, SnoN2 is the major species in most tissues, but SnoN and SnoN2 are ex pressed at approximately equal levels in brain. In human tissues, SNON 2 is the less abundantly expressed isoform. Expression of mouse SnoN a nd SnoN2 mRNAs is induced with immediate early kinetics upon serum sti mulation of quiescent fibrobrasts, even in the presence of the protein synthesis inhibitor cycloheximide, while Ski is not, Interestingly, a lthough both isoforms of Sno are induced, SnoN2 induction is much high er than SnoN, These data are consistent with a role for Sno in the res ponse to proliferation stimuli.