Proteomic Analysis Reveals a Role for the GTPase RPAP4/GPN1 and the Cochaperone RPAP3 in Biogenesis of All Three Nuclear RNA Polymerases
Biogenesis of nuclear RNA polymerases (RNAP) is a poorly understood, yet central molecular process in eukaryotes. Recent analysis of interaction partners of RNAP II, the enzyme that synthesizes protein-coding mRNAs, in the soluble fraction of cell extracts identified a series of factors that play central roles in RNAP II biogenesis. The GPN loop GTPase RPAP4/GPN1 was shown to be required for nuclear import of RNAP II, and the HSP90 co-factor RPAP3 is essential for cytoplasmic assembly of this multisubunit enzyme. Examination of the list of interactors for RNAP II as well as RPAP4/GPN1 and RPAP3 reveals the presence of many specific subunits of RNAP I and III, which synthesize most of the cell’s non-coding transcripts. This finding suggests that biogenesis of all three nuclear RNAPs may be coupled. Silencing of RPAP4/GPN1 and RPAP3 further indicates that both factors are essential for normal nuclear localization of the three polymerases. We present a model in which biogenesis of RNAP I, II and III is integrated through the action of assembly and nuclear import factors.
KeywordsRNA polymerase RNA polymerase II-associated proteins (RPAP) Biogenesis Nuclear import Assembly
We wish to thank members of our laboratory for helpful discussions. This work was supported by grants from the Fonds de la recherche en santé du Québec (FRSQ) and the Canadian Institutes for Health Research (CIHR).
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