The exoribonuclease Dis3L2 defines a novel eukaryotic RNA degradation pathway.

The final step of cytoplasmic mRNA degradation proceeds in either a 5'-3' direction catalysed by Xrn1 or in a 3'-5' direction catalysed by the exosome. Dis3/Rrp44, an RNase II family protein, is the catalytic subunit of the exosome. In humans, there are three paralogues of this enzyme: DIS3, DIS3L, and DIS3L2. In this work, we identified a novel Schizosaccharomyces pombe exonuclease belonging to the conserved family of human DIS3L2 and plant SOV. Dis3L2 does not interact with the exosome components and localizes in the cytoplasm and in cytoplasmic foci, which are docked to P-bodies. Deletion of dis3l2(+) is synthetically lethal with xrn1Δ, while deletion of dis3l2(+) in an lsm1Δ background results in the accumulation of transcripts and slower mRNA degradation rates. Accumulated transcripts show enhanced uridylation and in vitro Dis3L2 displays a preference for uridylated substrates. Altogether, our results suggest that in S. pombe, and possibly in most other eukaryotes, Dis3L2 is an important factor in mRNA degradation. Therefore, this novel 3'-5' RNA decay pathway represents an alternative to degradation by Xrn1 and the exosome.