ࡱ > [ ] T U V W X Y Z 5@ v bjbj22 X X 4 j $ e e e P f j k o ( o o o p p p ş ǟ ǟ ǟ ǟ ǟ ǟ $ R 0 ( p * p p p q o o q $ o o + p ş $ ) ) o k & e , ) $ l ) B 1 B ) ) z B 6 d p p p d0 p6 D/ p6 The human core exosome interacts with differentially localized processive RNases: hDIS3 and hDIS3L
Rafal Tomecki1,2, Maiken S. Kristiansen3,5, Sren Lykke-Andersen3,5, Aleksander Chlebowski2,5, Katja M. Larsen4, Roman J. Szczesny1,2, Karolina Drazkowska1,2, Agnieszka Pastula2,6, Jens S. Andersen4, Piotr P. Stepien1,2, Andrzej Dziembowski1,2,* and Torben Heick Jensen 3,*
1Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul. Pawinskiego 5a, 02-106 Warsaw, Poland, 2Department of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, ul. Pawinskiego 5a, 02-106 Warsaw, Poland, 3Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, Aarhus University, C. F. Mllers All, Bldg. 1130, DK-8000 Aarhus C, Denmark, 4Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Campusvej 55, DK-5230 Odense, Denmark
*Correspondence to:
Andrzej Dziembowski, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul. Pawinskiego 5a, 02-106 Warsaw, Poland. Tel.: +48 22 59220323337; Fax: +48 22 6584176; E-mail: HYPERLINK "mailto:andrzejd@ibb.waw.pl"andrzejd@ibb.waw.pl
Torben Heick Jensen, Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, Aarhus University, C. F. Mllers All, Bldg. 1130, DK-8000 Aarhus C, Denmark. Tel.: +45 60202705; Fax: +45 86196500; E-mail: HYPERLINK "mailto:thj@mb.au.dk"thj@mb.au.dk
5These authors contributed equally to this work
6Present address: Department of Immunology, Jagiellonian University Medical College, ul, . Czysta 18, 31-121 Cracow, Poland
Running Title: Exonucleases Ribonucleases interacting with the human exosome
The eukaryotic RNA exosome is a ribonucleolytic complex involved in RNA processing and turnover. It consists of a nine-subunit catalytically inert core that serves a structural role and participates in substrate recognition. Best defined in Saccharomyces cerevisiae, enzymatic activity comes from the associated subunits Dis3p (Rrp44p) and Rrp6p. The former is a nuclear and cytoplasmic RNase II/R-like enzyme, which possesses both processive exo- and endonuclease activities, while the latter is a distributive RNase D-like nuclear exonuclease. Although the exosome core is highly conserved, identity and arrangements of its catalytic subunits in different vertebrates remain elusive. Here we demonstrate the association of two different Dis3p homologs hDIS3 and hDIS3L with the human exosome core. Interestingly, these factorsy display markedly different intracellular localizations;: in that hDIS3 is mainly nuclear, while hDIS3L is strictly cytoplasmic. This compartmental distribution reflects the substrate preferences of the complex in vivo. Both hDIS3 and hDIS3L are active exonucleases, however, only hDIS3 has retained endonucleolytic activity. Our data suggest that three different ribonucleases can serve as catalytic subunits for the exosome in human cells.
Subject category: RNA
Keywords: human exosome / RNA degradationribonuclease / RNB domain / RNase II/R enzymes / ribonuclease / human exosome / RNA degradation / RNA processing
Introduction
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