What are the structures of spliceosomes?

The spliceosome serves as a molecular machine made up of five small nuclear RNPs (snRNPs) and various non-snRNP proteins. Spliceosomes consist of the U1, U2, U4, U5, and U6 snRNP subunits. The U1 snRNP recognizes the 5' splice site of introns in pre-mRNA molecules. It pairs with the sequence at the exon-intron region, helping to position the spliceosome at the beginning of the intron for the splicing process to occur. The U2 snRNP is involved in recognizing the branch point sequence within introns. This sequence contains an adenosine nucleotide that serves as the nucleophile in the first step of the splicing reaction. The U2 snRNA base pairs with the branch point sequence, facilitating the formation of the catalytically active spliceosome complex. The U4 snRNP is responsible for removing introns from pre-mRNA during the process of splicing. Initially, U4 and U6 snRNAs are base-paired with each other, forming a stable duplex. However, when the tri-snRNP interacts with the A complex during spliceosome assembly, the interaction between U4 and U6 is destabilized and the two become dissociated. As a result, the 5' end of the U6 snRNA can then base pair with the 5' splice site (5'ss) of the pre-mRNA. The U5 snRNA undergoes conformational changes that position it near the 5' splice site (5'ss) and the branch point sequence. During the splicing process, the U5 snRNA plays a central role in bringing together the exons that are to be ligated.

Examples of non-snRNP proteins within the spliceosome include the Prp8 protein and Prp19 complex. The Prp8 protein plays a key role in the catalytic activity of the spliceosome and is involved in stabilizing RNA-RNA interactions within the spliceosome. The Prp19 complex is involved in activating spliceosomes for catalysis.