U2AF1 Gene

The U2AF1 gene, U2AF1 stands for "U2 Small Nuclear RNA Auxiliary Factor 1" is a protein-coding gene located on chromosome 21q22.3 that encodes U2 auxiliary factor.

The U2AF1 gene belongs to the splicing factor SR gene family. It plays a critical role in both constitutive and enhancer-dependent splicing by mediating protein-protein interactions and protein-RNA interactions required for the accurate selection of 3' splice sites.

The U2 helper factor consists of a large and a small subunit is a so-called non-nRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. The U2AF1 gene encodes the small subunit of U2 small nuclear RNA auxiliary factor 1, which plays a critical role in both constitutive and enhancer-dependent RNA splicing by directly mediating interactions between the large subunit and enhancer-bound proteins.

U2AF1 is one of several spliceosome complex genes that are frequently mutated in a number of hematologic malignancies, particularly de novo myelodysplastic syndromes (MDS), as well as in solid tumors such as lung, uterine, and pancreatic cancers. Two hotspot mutations (S34 and Q157) occur within the two zinc finger domains of the U2AF1 protein. U2AF1 mutations in MDS are associated with an increased risk of conversion to secondary acute myeloid leukemia; however, the impact of these mutations on overall survival is controversial.

1. Hosono N (2019) Genetic abnormalities and pathophysiology of MDS. Int J Clin Oncol. 24:885-892.
2. Li B et al (2020) Prognostic significance of <i>U2AF1</i> mutations in myelodysplastic syndromes: a meta-analysis. J Int Med Res 48:300060519891013.
3. Smith MA et al (2019) U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies. Nat Cell Biol 21:640-650.
4. Palangat M et al (2019) The splicing factor U2AF1 contributes to cancer progression through a noncanonical role in translation regulation. Genes Dev 33: 482-497.