The yeast exosome and human PM-Scl are related complexes of 3 '-> 5 ' exonucleases

We previously identified a complex of 3' --> 5' exoribonucleases, designate d the exosome, that is expected to play a major role in diverse RNA process ing and degradation pathways. Further biochemical and genetic analyses have revealed six novel components of the complex. Therefore, the complex conta ins 11 components, 10 of which are predicted to be 3' --> 5' exoribonucleas es on the basis of sequence homology. Human homologs were identified for 9 of the 11 yeast exosome components, three of which complement mutations in the respective yeast genes. Two of the newly identified exosome components are homologous to known components of the PM-Scl particle, a multisubunit c omplex recognized by autoimmune sera of patients suffering from polymyositi s-scleroderma overlap syndrome. We demonstrate that the homolog of the Rrp4 p exosome subunit is also a component of the PM-Scl complex, thereby provid ing compelling evidence that the yeast exosome and human PM-Scl complexes a re functionally equivalent. The two complexes are similar in size, and bioc hemical fractionation and indirect immunofluorescence experiments show that , in both yeast and humans, nuclear and cytoplasmic forms of the complex ex ist that differ only by the presence of the Rrp6p/PM-Scl100 subunit exclusi vely in the nuclear complex.