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

doi:10.1038/s41467-017-02050-w

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Article number	1871
Pages (from-to)	1-15
Journal	Nature Communications
Volume	8
Issue number	1
Early online date	30 Nov 2017
DOIs	https://doi.org/10.1038/s41467-017-02050-w
Publication status	Published - 30 Nov 2017

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NDP52 activates nuclear_FILI_Accepted30Oct2017_GOLD VoRFinal published version, 4.37 MBLicence: CC BY

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abstract = "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.",

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AU - Fili, Natalia

AU - Hari-Gupta, Yukti

AU - Dos Santos, Ália

AU - Cook, Alexander

AU - Poland, Simon

AU - Ameer-Beg, Simon M.

AU - Parsons, Maddy

AU - Toseland, Christopher P.

PY - 2017/11/30

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AB - 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.

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NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription

Abstract

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