SNRNP SM PROTEINS SHARE 2 EVOLUTIONARILY CONSERVED SEQUENCE MOTIFS WHICH ARE INVOLVED IN SM PROTEIN-PROTEIN INTERACTIONS

The spliceosomal small nuclear ribonucleoproteins (snRNPs) Ut, U2, U4/ U6 and U5 share eight proteins B', B, D1, D2, D3, E, F and G which for m the structural core of the snRNPs, This class of common proteins pla ys an essential role in the biogenesis of the snRNPs, In addition, the se proteins represent the major targets for the so-called anti-Sm auto -antibodies which are diagnostic for systemic lupus erythematosus (SLE ), We have characterized the proteins F and G from HeLa cells by cDNA cloning, and, thus, all human Sm protein sequences are now available f or comparison, Similar to the D, B/B' and E proteins, the F and G prot eins do not possess any of the known RNA binding motifs, suggesting th at other types of RNA-protein interactions occur in the snRNP core. St rikingly, the eight human Sm proteins possess mutual homology in two r egions, 32 and 14 amino acids long, that we term Sm motifs 1 and 2, Th e Sm motifs are evolutionarily highly conserved in all of the putative homologues of the human Sm proteins identified in the data base, Thes e results suggest that the Sm proteins may have arisen from a single c ommon ancestor, Several hypothetical proteins, mainly of plant origin, that clearly contain the conserved Sm motifs but exhibit only compara tively low overall homology to one of the human Sm proteins, were iden tified in the data base, This suggests that the Sm motifs may also be shared by non-spliceosomal proteins, Further, we provide experimental evidence that the Sm motifs are involved, at least in part, in Sm prot ein-protein interactions, Specifically, we show by co-immunoprecipitat ion analyses of in vitro translated B' and D3 that the Sm motifs are e ssential for complex formation between B' and D3, Our finding that the Sm proteins share conserved sequence motifs may help to explain the f requent occurrence in patient sera of anti-Sm antibodies that cross-re act with multiple Sm proteins and may ultimately further our understan ding of how the snRNPs act as auto-antigens and immunogens in SLE.