U2 snRNP B′′ Activators

U2 snRNP B'', also known as splicing factor U2 auxiliary factor 65 kDa subunit (U2AF65), is a protein that plays a critical role in the pre-mRNA splicing process. It is encoded by the U2AF2 gene in humans. U2AF65 is a component of the U2 small nuclear ribonucleoprotein (snRNP), which is essential for the recognition and removal of introns from pre-mRNA transcripts.The protein functions by binding to the polypyrimidine tract, a sequence of nucleotides located near the 3' splice site of introns. This binding facilitates the recruitment of other splicing factors and the assembly of the spliceosome, a large and dynamic complex responsible for catalyzing the splicing reactions. Through its role in spliceosome assembly, U2AF65 is involved in defining the boundaries between exons and introns, ensuring that splicing occurs precisely and that the resulting mRNA is correctly processed for translation into proteins.

U2AF65 contains two RNA recognition motifs (RRMs) that are responsible for its interaction with RNA, as well as a C-terminal domain that interacts with other splicing factors, such as U2AF35 and the SF1/mBBP protein. These interactions are vital for the stabilization of the early spliceosomal complex and the accurate recognition of splice sites.Mutations or dysregulation of U2AF65 have been linked to various human diseases, including cancer, where aberrant splicing events can lead to the production of oncogenic protein isoforms. The study of U2AF65 and its interaction with other splicing factors is therefore not only fundamental to our understanding of gene expression regulation but also has significant implications for the development of strategies targeting splicing in disease contexts.