U2 Small Nuclear RNA Auxiliary Factor 1 (U2AF1) is a crucial component of the spliceosome, a complex responsible for the removal of introns from pre-mRNA. This protein plays a significant role in RNA splicing, a process essential for the proper expression of genes. U2AF1 is a non-snRNP (small nuclear ribonucleoprotein) protein that is required for the binding of U2 snRNP to the pre-mRNA branch site .
U2AF1 is a subunit of the U2 Auxiliary Factor complex, which also includes a larger subunit known as U2AF2. The U2AF1 protein is approximately 35 kDa in size and is encoded by the U2AF1 gene located on chromosome 21q22.3 . The primary function of U2AF1 is to recognize and bind to AG nucleotides at the 3’ splice site, facilitating the assembly of the spliceosome .
RNA splicing is a critical step in the post-transcriptional modification of RNA. U2AF1, along with U2AF2, ensures the accurate removal of introns and the joining of exons to form mature mRNA. This process is vital for the generation of functional proteins. U2AF1 directly mediates interactions between the large subunit (U2AF2) and proteins bound to enhancers, playing a critical role in both constitutive and enhancer-dependent RNA splicing .
Mutations in the U2AF1 gene have been associated with various hematologic malignancies, particularly myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) . These mutations often occur at two hotspot locations, S34 and Q157, within the zinc-finger domains of the U2AF1 protein . Such mutations can lead to altered splicing patterns, contributing to the pathogenesis of these diseases .
Recombinant U2AF1 protein is used in various research applications to study its role in RNA splicing and its implications in disease. Understanding the function and regulation of U2AF1 can provide insights into the mechanisms of splicing-related disorders and potentially lead to the development of targeted therapies .