Dox-repressing P TET -PRE1, a 20S proteasome core component, inhibited BMV RNA replication by 70% ( Fig. 3 and Table 5 ). Similarly, repressing P TET -RPT6, one of six ATPases of the 19S regulatory particle of the 26S proteasome, resulted in an ,90% reduction in BMV RNA replication ( Fig. 3 and Table 5 ). Additionally, BMV 2a Pol accumulation increased significantly in both P TET -PRE1 and P TET -RPT6 dox-repressed cells (Fig. 5) . These results are consistent with previous findings that multiple non-essential ubiquitin-proteasome system components contribute to BMV RNA replication and that cells lacking PRE9, the only non-essential 20S proteasome component, also exhibit a substantial increase in BMV 2a Pol levels [9] . Our prior data show that having a substantial excess of 2a Pol shifts replication compartments from small spherular compartments to double membrane layers, but does not inhibit viral RNA replication [57] . Thus, the increase in 2a Pol accumulation in dox-repressed P TET -PRE1 and P TET -RPT6 (Fig. 5) is not likely the cause of decreased RNA replication. However, prior results do not exclude the possibility that PRE1 and RPT6 depletion might affect BMV RNA replication by directly or indirectly modulating 2a Pol localization, post-translational modification or interacting partners. The 26S proteasome localizes predominantly to the nuclear envelope-ER network [58] , the site of BMV RNA replication [16, 59] , and numerous viruses utilize the ubiquitin-proteasome system to facilitate infection or replication [60, 61, 62, 63, 64, 65] . Studies to define the specific role(s) of the ubiquitin-proteasome system in BMV RNA replication are ongoing.