NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription.

Natalia Fili, Yukti Hari-Gupta, Ália Dos Santos, Alexander Cook, Simon Poland, Simon M Ameer-Beg, Maddy Parsons, Christopher P Toseland

Nature communications 2017 Nov 30

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Myosin VI (MVI) has been found to be overexpressed in ovarian, breast and prostate cancers. Moreover, it has been shown to play a role in regulating cell proliferation and migration, and to interact with RNA Polymerase II (RNAPII). Here, we find that backfolding of MVI regulates its ability to bind DNA and that a putative transcription co-activator NDP52 relieves the auto-inhibition of MVI to enable DNA binding. Additionally, we show that the MVI-NDP52 complex binds RNAPII, which is critical for transcription, and that depletion of NDP52 or MVI reduces steady-state mRNA levels. Lastly, we demonstrate that MVI directly interacts with nuclear receptors to drive expression of target genes, thereby suggesting a link to cell proliferation and migration. Overall, we suggest MVI may function as an auxiliary motor to drive transcription.

Citation

Natalia Fili, Yukti Hari-Gupta, Ália Dos Santos, Alexander Cook, Simon Poland, Simon M Ameer-Beg, Maddy Parsons, Christopher P Toseland. NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription. Nature communications. 2017 Nov 30;8(1):1871