Title: Crystal structure of human spliceosomal U1 snRNP at 5.5 Å resolution
Abstract: Human spliceosomal U1 small nuclear ribonucleoprotein particles (snRNPs), which consist of U1 small nuclear RNA and ten proteins, recognize the 5′ splice site within precursor messenger RNAs and initiate the assembly of the spliceosome for intron excision. An electron density map of the functional core of U1 snRNP at 5.5 Å resolution has enabled us to build the RNA and, in conjunction with site-specific labelling of individual proteins, to place the seven Sm proteins, U1-C and U1-70K into the map. Here we present the detailed structure of a spliceosomal snRNP, revealing a hierarchical network of intricate interactions between subunits. A striking feature is the amino (N)-terminal polypeptide of U1-70K, which extends over a distance of 180 Å from its RNA binding domain, wraps around the core domain consisting of the seven Sm proteins and finally contacts U1-C, which is crucial for 5′-splice-site recognition. The structure of U1 snRNP provides insights into U1 snRNP assembly and suggests a possible mechanism of 5′-splice-site recognition. In eukaryotes, many genes contain one or more introns — sequences that are transcribed as part of the mRNA, but which are removed before the mRNA is translated into protein. The macromolecular machine that clips these introns at appropriate places in the precursor mRNA (pre-mRNA) is called the spliceosome. It consists of several RNA–protein complexes called snRNPs (small nuclear ribonucleoprotein particles or 'snurps'), as well as other non-snRNP proteins. The structure of the U1 snRNP, which assembles at the 5′ end of the intron and is the first snurp bound to a pre-mRNA, has now been determined to 5.5 Å resolution. The subunit interactions that emerge from the structure reveal how the start of the intron is recognized by U1 snRNP, thereby initiating its removal by the spliceosome. In eukaryotes, many genes contain one or more introns — sequences that are transcribed into mRNA, but which are then excised before the mRNA is translated into protein. Multiprotein–RNA complexes called snRNPs are the machinery that clips these introns out. This study presents the structure of the U1 snRNP, which assembles at the 5′ end of the intron; the subunit interactions suggest a model by which the snRNP is assembled and the 5′ splice site is recognized.