A yeast exosome cofactor, Mpp6, functions in RNA surveillance and in the degradation of noncoding RNA transcripts

Cosmin Saveanu (1) , Juri Rappsilber (2) , Hugo Ceulemans (3) , Alain Jacquier (1) , David Tollervey (2) , Laura Milligan (2) , Laurence Decourty (1)

1 Génétique des Interactions Macromoléculaires
2 Wellcome Trust Centre for Cell Biology
3 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven

A genome-wide screen for synthetic lethal (SL) interactions with loss of the nuclear exosome cofactors Rrp47/Lrp1 or Air1 identified 3'―\textgreater5' exonucleases, the THO complex required for mRNP assembly, and Ynr024w (Mpp6). SL interactions with mpp6Delta were confirmed for rrp47Delta and nuclear exosome component Rrp6. The results of bioinformatic analyses revealed homology between Mpp6 and a human exosome cofactor, underlining the high conservation of the RNA surveillance system. Mpp6 is an RNA binding protein that physically associates with the exosome and was localized throughout the nucleus. The results of functional analyses demonstrated roles for Mpp6 in the surveillance of both pre-rRNA and pre-mRNAs and in the degradation of "cryptic" noncoding RNAs (ncRNAs) derived from intergenic regions and the ribosomal DNA spacer heterochromatin. Strikingly, these ncRNAs are also targeted by other exosome cofactors, including Rrp47, the TRAMP complex (which includes Air1), and the Nrd1/Nab3 complex, and are degraded by both Rrp6 and the core exosome. Heterochromatic transcripts and other ncRNAs are characterized by very rapid degradation, and we predict that functional redundancy is an important feature of ncRNA metabolism.

Keywords: Post-Transcriptional; RNA Precursors; RNA Processing; Amino Acid Sequence; Cell Nucleus; Gene Expression Regulation; Fungal; Humans; Molecular Sequence Data; Mutation; Protein Binding; RNA-Binding Proteins; RNA; Messenger; RNA Stability; Untranslated; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Sequence Homology; Amino Acid

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Molecular biology

Cosmin Saveanu, Juri Rappsilber, Hugo Ceulemans, Alain Jacquier, David Tollervey, et al.. A yeast exosome cofactor, Mpp6, functions in RNA surveillance and in the degradation of noncoding RNA transcripts. Molecular and Cellular Biology, 2008, 28 (17), pp.5446--5457. ⟨10.1128/MCB.00463-08⟩. ⟨pasteur-01404695⟩