The yeast nuclear exosome contains multiple 3'-->5' exoribonucleases, raisi
ng the question of why so many activities are present in the complex. All c
omponents are required during the 3' processing of the 5.8S rRNA, together
with the putative RNA helicase Dob1p/R/Mtr4p. During this processing three
distinct steps can be resolved, and hand-over between different exonuclease
s appears to occur at least twice. 3' processing of snoRNAs (small nucleola
r RNAs) that are excised from polycistronic precursors or from mRNA introns
is also a multi-step process that involves the exosome, with final trimmin
g specifically dependent on the Rrp6p component. The spliceosomal U4 snRNA
(small nuclear RNA) is synthesized from a 3' extended precursor that is cle
aved by Rntlp at sites 135 and 169 nt downstream of the mature 3' end. This
cleavage is followed by 3'-->5' processing of the pre-snRNA involving the
exosome complex and Dob1p. The exosome, together with Rntlp, also participa
tes in the 3' processing of the U1 and U5 snRNAs, We conclude that the exos
ome is involved in the processing of many RNA substrates and that different
components can have distinct functions.