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

Mol Biol Cell. 2006 Jan;17(1):460-74. doi: 10.1091/mbc.e05-09-0848. Epub 2005 Oct 26.


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 Deltagrn1 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 deltagrn1 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Cell Nucleolus / genetics*
  • Cell Nucleolus / metabolism*
  • Cell Proliferation
  • Conserved Sequence
  • GTP Phosphohydrolases / chemistry
  • GTP Phosphohydrolases / classification
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins
  • Gene Deletion
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Mutation / genetics
  • Nuclear Proteins
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Precursors / genetics*
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / classification
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Sequence Alignment


  • GNL3L protein, human
  • Nuclear Proteins
  • RNA Precursors
  • Ribosomal Proteins
  • Schizosaccharomyces pombe Proteins
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Grn1 protein, S pombe