title: NVL2, a nucleolar AAA-ATPase, is associated with the nuclear exosome and is involved in pre-rRNA processing.
abstract: Nuclear VCP-like 2 (NVL2) is a member of the chaperone-like AAA-ATPase family and is involved in the biosynthesis of 60S ribosomal subunits in mammalian cells. We previously showed the interaction of NVL2 with a DExD/H-box RNA helicase MTR4/DOB1, which is a known cofactor for an exoribonuclease complex, the exosome. This finding implicated NVL2 in RNA metabolic processes during ribosome biogenesis. In the present study, we found that a series of mutations within the ATPase domain of NVL2 causes a defect in pre-rRNA processing into mature 28S and 5.8S rRNAs. Co-immunoprecipitation analysis showed that NVL2 was associated with the nuclear exosome complex, which includes RRP6 as a nucleus-specific catalytic subunit. This interaction was prevented by depleting either MTR4 or RRP6, indicating their essential role in mediating this interaction with NVL2. Additionally, knockdown of MPP6, another cofactor for the nuclear exosome, also prevented the interaction by causing MTR4 to dissociate from the nuclear exosome. These results suggest that NVL2 is involved in pre-rRNA processing by associating with the nuclear exosome complex and that MPP6 is required for maintaining the integrity of this rRNA processing complex.
authors.affiliation: Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima 770-8506, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshikatsu
authors.affiliation: Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Yo-ichi
authors.initials: Y
authors.lastname: Ishida
authors.affiliation: Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Sudo
authors.affiliation: Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima 770-8506, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Yuasa
authors.affiliation: Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima 770-8506, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan. Electronic address: nagahama@my-pharm.ac.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Nagahama
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D002467:Cell Nucleus / Q000378:metabolism; D005095:Exoribonucleases / Q000378:metabolism; D063326:Exosome Multienzyme Ribonuclease Complex / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000378:metabolism; D034622:RNA Interference; D012322:RNA Precursors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D054683:Ribosome Subunits, Large, Eukaryotic / Q000378:metabolism
chemical_list: C496472:MPP6 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D012322:RNA Precursors; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C077044:EXOSC10 protein, human; D000251:Adenosine Triphosphatases; C512513:MTREX protein, human; D000074183:ATPases Associated with Diverse Cellular Activities; C500249:NVL protein, human; D020365:RNA Helicases
keywords: AAA-ATPase; NVL2; Pre-rRNA processing; RNA exosome; Ribosome biogenesis