Premium
Nuclear import of RNA polymerase II requires the conserved GPN‐loop GTPase XAB1/GPN1
Author(s) -
Lacombe AndreeAnne,
Forget Diane,
Cloutier Philippe,
AlKhoury Racha,
Bouchard Annie,
LavalleeAdam Mathieu,
Jeronimo Celia,
Archambault Jacques,
Blanchette Mathieu,
Coulombe Benoit
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.860.1
Subject(s) - ran , microbiology and biotechnology , biology , rna polymerase ii , nuclear transport , cytoplasm , transcription (linguistics) , gtpase , cell nucleus , gene , genetics , gene expression , promoter , linguistics , philosophy
Over the past 3 decades, many efforts have been made to identify and characterize the factors that regulate the activity of RNA polymerase II (RNAPII), the enzyme that synthesizes all the mRNA and many small nuclear RNA in eukaryotes. Quite surprisingly, very little is known about the cell machinery that regulates the fate of RNAPII before or after transcription. In this study, we report that XAB1/GPN1, a member of a unique class of GTPases containing a conserved GPN‐loop, is involved in the biogenesis of RNAPII by regulating its nuclear import. XAB1/GPN1 is physically associated with RNAPII in the soluble cell fraction and is essential for cell growth. Accumulation of RNAPII in the cytoplasm of the cell was induced upon (i) depletion of XAB1/GPN1 by siRNA silencing, (ii) overexpression of a XAB1‐GFP dominant negative fusion protein, (iii) mutation of the GTP‐binding or GPN motifs of the XAB1/GPN1 homologue in yeast, NPA3, and (iv) treatment of cells with leptomycin B, an inhibitor of XPO1/CRM1‐dependent nuclear export. Yeast strains with mutations in the NPA3 gene showed hypersensitivity to benomyl, a specific inhibitor of microtubule assembly, suggesting a role for microtubules in RNAPII biogenesis. Together, these results indicate that XAB1/GPN1 shuttles between the cytoplasm and the nucleus to mediate nuclear import of RNAPII.