The Homologous Putative GTPases Grn1p from Fission Yeast and the Human GNL3L Are Required for Growth and Play a Role in Processing of Nucleolar Pre-rRNA
- 1 January 2006
- journal article
- research article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 17 (1) , 460-474
- https://doi.org/10.1091/mbc.E05-09-0848
Abstract
Grn1p from fission yeast and GNL3L from human cells, two putative GTPases from the novel HSR1_MMR1 GTP-binding protein subfamily with circularly permuted G-motifs play a critical role in maintaining normal cell growth. Deletion of Grn1 resulted in a severe growth defect, a marked reduction in mature rRNA species with a concomitant accumulation of the 35S pre-rRNA transcript, and failure to export the ribosomal protein Rpl25a from the nucleolus. Deleting any of the Grn1p G-domain motifs resulted in a null phenotype and nuclear/nucleolar localization consistent with the lack of nucleolar export of preribosomes accompanied by a distortion of nucleolar structure. Heterologous expression of GNL3L in a Δgrn1 mutant restored processing of 35S pre-rRNA, nuclear export of Rpl25a and cell growth to wild-type levels. Genetic complementation in yeast and siRNA knockdown in HeLa cells confirmed the homologous proteins Grn1p and GNL3L are required for growth. Failure of two similar HSR1_MMR1 putative nucleolar GTPases, Nucleostemin (NS), or the dose-dependent response of breast tumor autoantigen NGP-1, to rescue Δgrn1 implied the highly specific roles of Grn1p or GNL3L in nucleolar events. Our analysis uncovers an important role for Grn1p/GNL3L within this unique group of nucleolar GTPases.Keywords
This publication has 77 references indexed in Scilit:
- Going in GTP cycles in the nucleolusThe Journal of cell biology, 2005
- A multistep, GTP-driven mechanism controlling the dynamic cycling of nucleosteminThe Journal of cell biology, 2005
- Comparative Genomics, Evolution and Origins of the Nuclear Envelope and Nuclear Pore ComplexCell Cycle, 2004
- Insights into the evolution of the nucleolus by an analysis of its protein domain repertoireBioEssays, 2004
- [56] Molecular genetic analysis of fission yeast Schizosaccharomyces pombePublished by Elsevier ,2004
- The Pfam protein families databaseNucleic Acids Research, 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAsNature Genetics, 2003
- Classification and evolution of P-loop GTPases and related ATPasesJournal of Molecular Biology, 2002
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997
- Identification and characterization of a yeast nucleolar protein that is similar to a rat liver nucleolar protein.The Journal of cell biology, 1988