title: RNA degradation by the exosome is promoted by a nuclear polyadenylation complex.
abstract: The exosome complex of 3'-5' exonucleases participates in RNA maturation and quality control and can rapidly degrade RNA-protein complexes in vivo. However, the purified exosome showed weak in vitro activity, indicating that rapid RNA degradation requires activating cofactors. This work identifies a nuclear polyadenylation complex containing a known exosome cofactor, the RNA helicase Mtr4p; a poly(A) polymerase, Trf4p; and a zinc knuckle protein, Air2p. In vitro, the Trf4p/Air2p/Mtr4p polyadenylation complex (TRAMP) showed distributive RNA polyadenylation activity. The presence of the exosome suppressed poly(A) tail addition, while TRAMP stimulated exosome degradation through structured RNA substrates. In vivo analyses showed that TRAMP is required for polyadenylation and degradation of rRNA and snoRNA precursors that are characterized exosome substrates. Poly(A) tails stimulate RNA degradation in bacteria, suggesting that this is their ancestral function. We speculate that this function was maintained in eukaryotic nuclei, while cytoplasmic mRNA poly(A) tails acquired different roles in translation.
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK.
authors.forename: John
authors.initials: J
authors.lastname: LaCava
authors.forename: Jonathan
authors.initials: J
authors.lastname: Houseley
authors.forename: Cosmin
authors.initials: C
authors.lastname: Saveanu
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petfalski
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thompson
authors.forename: Alain
authors.initials: A
authors.lastname: Jacquier
authors.forename: David
authors.initials: D
authors.lastname: Tollervey
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D053487:DEAD-box RNA Helicases; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D013058:Mass Spectrometry; D020411:Oligonucleotide Array Sequence Analysis; D026723:Polyadenylation; D011062:Polynucleotide Adenylyltransferase / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D020365:RNA Helicases / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D020871:RNA Stability; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C415825:Air2 protein, S cerevisiae; D002352:Carrier Proteins; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; D012319:RNA Polymerase II; D011062:Polynucleotide Adenylyltransferase; D004259:DNA-Directed DNA Polymerase; C487545:PAP2 protein, S cerevisiae; C101004:MTR4 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases