title: Air proteins control differential TRAMP substrate specificity for nuclear RNA surveillance.
abstract: RNA surveillance systems function at critical steps during the formation and function of RNA molecules in all organisms. The RNA exosome plays a central role in RNA surveillance by processing and degrading RNA molecules in the nucleus and cytoplasm of eukaryotic cells. The exosome functions as a complex of proteins composed of a nine-member core and two ribonucleases. The identity of the molecular determinants of exosome RNA substrate specificity remains an important unsolved aspect of RNA surveillance. In the nucleus of Saccharomyces cerevisiae, TRAMP complexes recognize and polyadenylate RNAs, which enhances RNA degradation by the exosome and may contribute to its specificity. TRAMPs contain either of two putative RNA-binding factors called Air proteins. Previous studies suggested that these proteins function interchangeably in targeting the poly(A)-polymerase activity of TRAMPs to RNAs. Experiments reported here show that the Air proteins govern separable functions. Phenotypic analysis and RNA deep-sequencing results from air mutants reveal specific requirements for each Air protein in the regulation of the levels of noncoding and coding RNAs. Loss of these regulatory functions results in specific metabolic and plasmid inheritance defects. These findings reveal differential functions for Air proteins in RNA metabolism and indicate that they control the substrate specificity of the RNA exosome.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Karyn
authors.initials: K
authors.lastname: Schmidt
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Xu
authors.forename: David H
authors.initials: DH
authors.lastname: Mathews
authors.forename: J Scott
authors.initials: JS
authors.lastname: Butler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D030781:Organisms, Genetically Modified; D011061:Poly A / Q000378:metabolism; D011485:Protein Binding; D020871:RNA Stability / Q000235:genetics / Q000502:physiology; D015138:RNA, Nuclear / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013379:Substrate Specificity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C415824:Air1 protein, S cerevisiae; C415825:Air2 protein, S cerevisiae; D015138:RNA, Nuclear; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D011061:Poly A; D063326:Exosome Multienzyme Ribonuclease Complex; C112610:RRP6 protein, S cerevisiae