XRN

XRN refers to a family of 5'-to-3' exoribonucleases that degrade RNA from the 5' end and are conserved in eukaryotes. The best-characterized members in animals are XRN1, which operates mainly in the cytoplasm, and XRN2, which is primarily nuclear. In budding yeast, the homologs are Xrn1 and Rat1, corresponding to cytoplasmic and nuclear functions respectively. XRN enzymes act on RNA substrates that present a 5' monophosphate; RNAs bearing a 5' cap or strong secondary structure often require prior decapping or remodeling to become substrates.

Functions of XRN enzymes include the cytoplasmic decay and turnover of mRNAs, surveillance of aberrant transcripts, and processing or degradation of certain noncoding RNAs. XRN2 participates in transcription termination of RNA polymerase II via a torpedo-like mechanism in which the enzyme degrades the nascent RNA after cleavage, aiding in polymerase release. Together with other RNA decay pathways, XRN activity helps regulate gene expression and maintain RNA quality control within the cell.

In addition to normal cellular roles, XRN activity influences responses to viral infection. Some viruses produce RNAs that can stall or evade XRN-mediated degradation, and cells may alter XRN function as part of antiviral defenses. The structure and biochemistry of XRN proteins reveal a catalytic core that supports highly processive degradation, with activity influenced by RNA end status and structure.

XRN enzymes are broadly studied as models of mRNA decay and transcription termination, and disruptions of XRN function have implications for gene expression regulation and cellular physiology. Related enzymes in bacteria, such as RNase J, provide functional analogs in 5'-to-3' RNA degradation, though they are not direct homologs.