Insights into splicing: structure of the yeast U1 snRNP

Abstract

Precursor‐mRNA splicing is catalyzed by a large and dynamic macromolecular assemblage termed the spliceosome. Integral to spliceosome function are five RNA‐protein complexes termed uridine‐rich small nuclear ribonucleoprotein particles, the U1, U2, U4, U5 and U6 snRNPs. An early and significant regulatory step in assembly of the spliceosome and splice‐site selection is U1 snRNP recognition of the junction between the 5′ exon and intron, a 5′ splice‐site. This pivotal event will act to: (1) trigger spliceosome assembly; (2) demarcate a 5′ splice‐site; and (3) contribute to spliceosome fidelity. In metazoans, U1 snRNP 5′ splice‐site selection is aided by transiently associated proteins known as alternative splicing factors that function to guide U1 snRNP to specific 5′ splice‐site(s). In contrast, Saccharomyces cerevisae has very few protein coding genes with more than a single intron. S. cerevisae U1 snRNP is an 18‐subunit, ~800 kDa assembly that has as integral subunits proteins that are alternative splicing factors in higher eukaryotes. We report the structure of a native S. cerevisae U1 snRNP determined by electron microscopy and present a working model that provides insight into the function of its protein subunits.Funding provided by the National Science Foundation; Howard Hughes Medical Institute