ABSTRACT
Transcription
and replication of the influenza virus RNA genome occur in the nuclei
of infected cells through the viral RNA-dependent RNA polymerase
consisting of PB1, PB2, and PA. We previously identified a
host factor designated RAF-1 (RNA polymerase activating factor 1) that
stimulates viral RNA synthesis. RAF-1 is found to be identical to
Hsp90. Here, we examined the intracellular localization of Hsp90 and
viral RNA polymerase subunits and their molecular interaction. Hsp90
was found to interact with PB2 and PB1, and it was relocalized to the
nucleus upon viral infection. We found that the nuclear transport of
Hsp90 occurs in cells expressing PB2 alone. The nuclear transport of
Hsp90 was in parallel with that of the viral RNA polymerase binary
complexes, either PB1 and PB2 or PB1 and PA, as well as with that of
PB2 alone. Hsp90 also interacted with the binary RNA polymerase complex
PB1-PB2, and it was dissociated from the PB1-PB2 complex upon its
association with PA. Furthermore, Hsp90 could form a stable
PB1-PB2-Hsp90 complex prior to the formation of a ternary polymerase
complex by the assembly of PA in the infected cells. These results
suggest that Hsp90 is involved in the assembly and nuclear transport of
viral RNA polymerase subunits, possibly as a molecular chaperone for
the polymerase subunits prior to the formation of a mature ternary
polymerase
complex.
RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits
