RNA exonuclease 5 (REXO5)

RNA exonuclease 5 (REXO5) is a highly conserved 3′→5′ single-stranded RNA exonuclease found in eukaryotes. It degrades RNA through its exoribonuclease domain and binds RNA via a paired RNA recognition motif (RRM). In mammals, REXO5 is notably enriched in testicular tissue, localizes to the nucleus/nucleolus, and requires a nuclear localization signal for its proper compartmentalization. Functionally, REXO5 participates in the maturation and degradation of RNA molecules and has critical roles in regulating genomic integrity through resolving R-loops—RNA/DNA hybrid structures—particularly in response to DNA damage. Loss of REXO5 leads to R-loop accumulation and heightened DNA damage response, with implications for cancer pathogenesis, especially in CML. REXO5 is evolutionarily related to the Rex protein family (such as REXO1 in yeast).

Other names

REXO5NEF-spLOC81691Exonuclease NEF-spRNA exonuclease 5putative RNA exonuclease NEF-sp44M2.3

Drugs targeting this molecule could act by inhibiting its exonuclease activity, disrupting R-loop regulation and DNA damage repair pathways; ATR inhibitors are more effective when REXO5 is knocked out.