title: The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities.
abstract: The eukaryotic exosome is a ten-subunit 3' exoribonucleolytic complex responsible for many RNA-processing and RNA-degradation reactions. How the exosome accomplishes this is unknown. Rrp44 (also known as Dis3), a member of the RNase II family of enzymes, is the catalytic subunit of the exosome. We show that the PIN domain of Rrp44 has endoribonucleolytic activity. The PIN domain is preferentially active toward RNA with a 5' phosphate, suggesting coordination of 5' and 3' processing. We also show that the endonuclease activity is important in vivo. Furthermore, the essential exosome subunit Csl4 does not contain any domains that are required for viability, but its zinc-ribbon domain is required for exosome-mediated mRNA decay. These results suggest that specific exosome domains contribute to specific functions, and that different RNAs probably interact with the exosome differently. The combination of an endoRNase and an exoRNase activity seems to be a widespread feature of RNA-degrading machines.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Texas Health Science Center-Houston, 6431 Fannin Street, MSB 1.212 Houston, Texas 77030, USA.
authors.forename: Daneen
authors.initials: D
authors.lastname: Schaeffer
authors.forename: Borislava
authors.initials: B
authors.lastname: Tsanova
authors.forename: Ana
authors.initials: A
authors.lastname: Barbas
authors.forename: Filipa Pereira
authors.initials: FP
authors.lastname: Reis
authors.forename: Eeshita Ghosh
authors.initials: EG
authors.lastname: Dastidar
authors.forename: Maya
authors.initials: M
authors.lastname: Sanchez-Rotunno
authors.forename: Cecília Maria
authors.initials: CM
authors.lastname: Arraiano
authors.forename: Ambro
authors.initials: A
authors.lastname: van Hoof
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D003593:Cytoplasm / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism*; D005095:Exoribonucleases / Q000378:metabolism*; D063326:Exosome Multienzyme Ribonuclease Complex; D055354:Exosomes / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D004722:Endoribonucleases; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; D012260:Ribonucleases; C542283:DIS3 protein, S cerevisiae