CONSERVATION OF REGULATED ALTERNATIVE SPLICING AND IDENTIFICATION OF FUNCTIONAL DOMAINS IN VERTEBRATE HOMOLOGS TO THE DROSOPHILA SPLICING REGULATOR, SUPPRESSOR-OF-WHITE-APRICOT

Although several splicing regulatory proteins have been identified in Drosophila through characterization of various genetic mutations, incl uding sex-lethal, transformer, transformer-2, suppressor-of-white-apri cot (su(w(a))), and possibly suppressor-of-sable, none of these have b een identified in vertebrates, We describe the cloning and characteriz ation of human (HsSWAP) and mouse (MmSWAP) homologs of the su(w(a)) ge ne. Comparison of the Drosophila and mammalian proteins reveals five h ighly homologous regions, including an arginine/serine rich domain and two repeated modules that are homologous to regions in the constituti ve splicing factor, SPP91/PRP21. These modules thus define a new motif likely important in the regulatory and constitutive splicing function s of these proteins. The Drosophila su(w(a)) gene autoregulates its ex pression by control of splicing of its first two introns. Comparison o f mammalian and Drosophila SWAP mRNAs revealed that the splice junctio ns of these regulated introns are precisely conserved, showing definit ively that these genes are ancestrally related. Moreover, mammalian SW AP mRNAs are also alternatively spliced at the same splice sites, show ing that mammalian SWAP expression is regulated (presumably autogenous ly) by control of splicing of these two introns. These several structu ral features therefore strongly suggest that the mammalian SWAP gene f unctions as a vertebrate alternative splicing regulator.