Actin is abundant in the nucleus and it is clear that nuclear actin has important functions. However, mystery surrounds the absence of classical actin filaments in the nucleus. To address this question, we investigated how polymerizing nuclear actin into persistent nuclear actin filaments affected transcription by RNA polymerase II. Nuclear filaments impaired nuclear actin dynamics by polymerizing and sequestering nuclear actin. Polymerizing actin into stable nuclear filaments disrupted the interaction of actin with RNA polymerase II and correlated with impaired RNA polymerase II localization, dynamics, gene recruitment, and reduced global transcription and cell proliferation. Polymerizing and crosslinking nuclear actin in vitro similarly disrupted the actin–RNA-polymerase-II interaction and inhibited transcription. These data rationalize the general absence of stable actin filaments in mammalian somatic nuclei. They also suggest a dynamic pool of nuclear actin is required for the proper localization and activity of RNA polymerase II.
The authors declare no competing or financial interests.
L.A.S. and P.deL. conceived of experiments; L.A.S., M.P., P.A., C.M.C. and K.L. conducted experiments. E.G., D.S.K., S.T.K., C.J.G. and P.deL. supervised and/or contributed to the design of experiments; L.A.S., G.J.G. and P.deL. analyzed the data and wrote the manuscript.
This work was supported by the National Institutes of Health (NIH) [grant numbers GM80587 to P.deL., GM076561 to C.J.G., GM114666 to D.S.K. and GM076516 and GM103540 to E.G.]; the Chicago Biomedical Consortium with support from the Searle Funds at the Chicago Community Trust (to P.deL. and S.T.K.); the Northwestern University Physical Sciences Oncology Center associated with National Cancer Institute [grant number U54CA143869 to C.J.G., P.deL. and S.T.K.]; the American Heart Association (AHA) [grant numbers 13IRG14780028 to D.S.K. and 13PRE17050060 to L.A.S.]; a Chicago Biomedical Consortium Scholar award (to L.A.S.); a University of Illinois at Chicago (UIC) Dean's Scholar and Chancellor's graduate research fellowship (to L.A.S.); and a UIC CM Craig Fellowship (to M.P.). Deposited in PMC for release after 12 months.
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.195867.supplemental
- Received July 25, 2016.
- Accepted July 27, 2016.
- © 2016. Published by The Company of Biologists Ltd