Small Nuclear RNA - SnRNA in The Spliceosome

SnRNA in The Spliceosome

Spliceosomes are a major component of an integral step in eukaryotic precursor messenger RNA maturation. A mistake in even a single nucleotide can be devastating to the cell, and a reliable, repeatable method of RNA processing is necessary to ensure cell survival. The spliceosome is a large, protein-RNA complex that consists of five small nuclear RNAs (U1, U2, U4, U5, and U6) and over 150 proteins. The snRNAs, along with their associated proteins, form ribonucleoprotein complexes (snRNPs), which bind to specific sequences on the pre-mRNA substrate. This intricate process results in two sequential transesterification reactions. These reactions will produce a free lariat intron and ligate two exons to form a mature mRNA. There are two separate classes of spliceosomes. The major class, which is far more abundant in eukaryotic cells, splices primarily U2-type introns. The initial step of splicing is the bonding of the U1 snRNP and its associated proteins to the 5’ splice end to the hnRNA. This creates the commitment complex which will constrain the hnRNA to the splicing pathway. Then, U2 snRNP is recruited to the spliceosome binding site and forms complex A. U2 snRNP changes the confirmation of the hnRNA-snRNP complex, exposing the nucleotide favorably for splicing. Following the confirmation change, the U4/U5/U6 tri-snRNP complex binds to complex A to form the structure known as complex B. After rearrangement, complex C is formed, and the spliceosome is active for catalysis.

In addition to this main spliceosome complex, there exists a much less common (~1%) minor spliceosome. This complex comprises U11, U12, U4atac, U6atac and U5 snRNPs. These snRNPs are functional analogs of the snRNPs used in the major spliceosome. The minor spliceosome splices U-12 type introns. The two types of introns mainly differ in their splicing sites: U2-type introns have GT-AG 5’ and 3’ splice sites while U12-type introns have AT-AC at their 5’ and 3’ ends. The minor spliceosome carries out its function through a different pathway from the major spliceosome.