5'-3' Exoribonuclease 2 (XRN2)

5'-3' Exoribonuclease 2 (XRN2) is a highly conserved nuclear enzyme, encoded by the XRN2 gene in humans, which performs 5'→3' exonucleolytic degradation of RNA substrates possessing a 5' monophosphate group. XRN2 plays a critical role in eukaryotic RNA metabolism, particularly in the termination of mRNA transcription by RNA polymerase II—as described in the torpedo model—where XRN2 degrades the downstream cleavage product and forcibly dissociates the polymerase from DNA. It is also active in ribosomal RNA maturation, telomere maintenance, and overall nuclear RNA surveillance, thereby preventing accumulation of potentially deleterious or aberrant RNA species. Defects or depletion of XRN2 result in major transcriptional and developmental abnormalities. The enzyme’s structure features a conserved active site requiring divalent cations (Mg²⁺ or Mn²⁺), and it typically interacts with protein cofactors (such as Rai1 in yeast, and XTBD-containing proteins in mammals) to regulate its stability and function[1][2][4][5][3][6].

Other names

Dhp proteinDhm1-like proteinRAT1 (yeast)XRN2

For hypothetical or investigative drugs: inhibition or modulation of XRN2 would primarily affect nuclear 5'→3' RNA decay pathways, disrupt transcription termination, and alter RNA surveillance mechanisms[4]. Drugs impacting related nucleases (DCP1a/DCP2, TTF2) or RNA polymerase II function may have indirect effects on XRN2’s pathway[4].