SM AND SM-LIKE PROTEINS BELONG TO A LARGE FAMILY - IDENTIFICATION OF PROTEINS OF THE U6 AS WELL AS THE U1, U2, U4 AND U5 SNRNPS

Several small nuclear RNAs (snRNAs), including the spliceosomal U1, U2 , U4 and U5 snRNAs, are associated with Sm proteins. These eight small proteins form a heteromeric complex that binds to snRNAs and plays a major role in small nuclear ribonucleoprotein (snRNP) biogenesis and t ransport. These proteins are also a major target for autoantibodies in the human disease systemic lupus erythematosus, By sequence compariso n I have shown that all the known Sm proteins share a common structura l motif which might explain their immunological cross-reactivity. Data base searches using this motif uncovered a large number of Sm-like pro teins from plants, animals and fungi. These proteins have been grouped in at least 13 different subfamilies. Genes encoding divergent yeast members were cloned and used to produce tagged fusion proteins. Some o f these proteins are canonical Sm proteins as they associate with the yeast U1, U2, U4/U6 and U5 snRNAs. Surprisingly, one Sm-like protein w as found to be a component of the U6 snRNP. These findings have implic ations for the structure of the Sm protein complex, spliceosomal snRNP evolution, snRNA transport and modification as well as the involvemen t of Sm proteins in systemic lupus erythematosus.