Are snRNPs involved in splicing?

Abstract

Discrete, stable small RNA molecules are found in the nuclei of cells¹ from a wide variety of eukaryotic organisms². Many of these small nuclear RNA (snRNA) species, which range in size from about 90 to 220 nucleotides, have been well-characterised biochemically^3–6, and some sequenced^7,8. However, their function has remained obscure. The most abundant snRNA species exist as a closely related set of RNA–protein complexes called small nuclear ribonucleoproteins (snRNPs)⁹. snRNPs are the antigens recognised by antibodies from some patients with lupus erythematosus (LE), an autoimmune rheumatic disease^10,11. Anti-RNP antibodies from lupus sera selectively precipitate snRNP species containing Ula⁷ and Ulb⁹ RNAs from mouse Ehrlich ascites cell nuclei, whereas anti-Sm antibodies bind these snRNPs and four others containing U2 (ref. 8), U4, US and U6 (ref. 9) RNAs. Both antibody systems precipitate the same seven prominent nuclear proteins (molecular weight 12,000–32,000). All molecules of the snRNAs U1, U2, U4, U5 and U6 appear to exist in the form of antigenic snRNPs⁹. The particles sediment at about 10S and each probably contains a single snRNA molecule. Indirect immunofluorescence studies (refs 12, 13, and unpublished observations) using anti-RNP and anti-Sm sera confirm the nuclear (but non-nucleolar) location of the antigenic snRNPs. Here we present several lines of evidence that suggest a direct involvement of snRNPs in the splicing of hnRNA. Most intriguing is the observation that the nucleotide sequence at the 5′ end of U1 RNA exhibits extensive complementarity to those across splice junctions in hnRNA molecules.