The 5'->3' Exoribonuclease (XRN) Project

The 5'->3' exoribonucleases (XRNs) comprise a large family of conserved enzymes in eukaryotes with important functions in RNA metabolism and RNA interference, including quality control, degradation, transport, and maturation of ribosomal and small nucleolar RNAs.

XRN1 (175 kD) is primarily cytosolic and is involved in degradation of decapped mRNAs, nonsense mediated decay, microRNA decay and is essential for proper development.

XRN2 (115 kD) is primarily nuclear, and its ortholog in S. cerevisiae, more commonly known as Rat1, was initially shown to have roles in RNA trafficking (ribonucleic acid trafficking 1) from the nucleus to the cytoplasm. More recent studies have identified XRN2/Rat1 as the exoribonuclease that is essential for the 'torpedo' model of transcription termination by RNA polymerase II (Pol II).

The XRNs are found in most eukaryotes, and share two highly conserved regions in their sequences.

XRNs have processive exoribonuclease (with no endoribonuclease) activity towards RNA substrates with a 5' monophosphate group. In comparison, the activity towards RNAs with a 5' hydroxyl, triphosphate or cap is much lower. Both enzymes require divalent cations (Mg2+ or Mn2+) for activity.

The exoribonuclease activity of Rat1 is stimulated by Rai1. Strong sequence homologs of Rai1 are found in other fungal species. A weak sequence homolog of Rai1, known as Dom3Z, exists in mammals, although it does not associate with XRN2. The Rai1 proteins share no recognizable amino acid sequence homology with other proteins.

Major findings from this project

Publications from this project

Funding for this project

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