5′-3′ exoribonuclease 1 (XRN1)

5′-3′ exoribonuclease 1 (XRN1) is a highly conserved, cytoplasmic enzyme responsible for degrading RNA molecules in the 5′ to 3′ direction, after decapping. XRN1 ensures proper cellular RNA turnover by removing faulty, aberrant, or excess RNA and plays major roles in mRNA decay (including nonsense-mediated decay), microRNA turnover, ribosomal RNA maturation, and regulation of gene expression. XRN1 operates in quality control and regulatory RNA decay, utilizing single- and double-stranded RNA as substrates, but requires an exposed 5′ monophosphate. Its activity is modulated by interactions with co-factors such as Dcs1. Dysfunction, reduced activity, or mutation of XRN1 is associated with pathological states such as cancer (notably osteosarcoma), and it is essential for development and mitochondrial function in model organisms. While no direct drugs currently target XRN1, it remains an active area of research for novel RNA-targeted therapies[1][3][4][5][6].

Other names

XRN1SEP1Strand-exchange protein 1 homologPACMAN (in Drosophila)5′-3′ exoribonuclease 15'-3' exoribonuclease 1Strand-exchange protein 1XRN 5'→3' exoribonuclease

For hypothetical drugs/inhibitors: Blockade of 5′-3′ exoribonuclease activity. Stabilization of oncogenic or pathogenic RNA species. Modulation of tumor suppressor mRNA stability. Indirect modulation via decapping enzyme (e.g., Dcs1 interaction) and RNA decay pathways. Currently, mechanisms are inferred from genetic knockout/knockdown studies.