XRN2

XRN2, or 5'-to-3' exoribonuclease 2, is a highly conserved nuclear enzyme in the XRN family. It is the vertebrate and yeast homolog of Rat1 and is primarily localized in the nucleus, with substantial presence in the nucleoplasm and nucleolus. XRN2 functions as a key regulator of nuclear RNA metabolism and participates in multiple RNA processing pathways.

The enzyme catalyzes processive degradation of RNA in the 5' to 3' direction. It typically requires a 5' monophosphate to initiate decay and cannot directly digest capped RNAs; decapping or prior cleavage is needed to expose suitable substrates. In the nucleus, XRN2 targets various RNA species, contributing to quality control and turnover of aberrant transcripts, byproducts of RNA maturation, and other nuclear RNAs.

A central and well-characterized role of XRN2 is in transcription termination of RNA polymerase II transcripts via the torpedo model. After cleavage of a nascent transcript, XRN2 degrades the downstream RNA fragment, which promotes release of Pol II and termination of transcription. This activity bridges RNA decay pathways with transcriptional control. XRN2 also participates in ribosomal RNA and other noncoding RNA maturation processes through its exonuclease activity.

Structure and evolution: XRN2 belongs to the XRN family and contains conserved N- and C-terminal catalytic domains responsible for 5'-to-3' exonuclease activity, with activity depending on metal ions. The enzyme is evolutionarily conserved from yeast to humans, underscoring its essential role in RNA metabolism. In cells, XRN2 often operates alongside other RNA processing and surveillance factors.

Clinical and research notes: Given its essential role in transcription termination and RNA maturation, XRN2 dysfunction can broadly affect gene expression. It remains an active area of study in RNA surveillance, transcription termination, and ribosomal RNA processing.