The motor protein Myosin VI (MVI) moves along cellular actin filaments and is involved in vesicular membrane traffic, cell migration, and mitosis. It interacts with many protein partners, and thus its malfunction can lead to various diseases including cardiomyopathy, deafness and cancer. MVI has even been found to be overexpressed in ovarian, breast and prostate cancers. In a recent study from a University of Kent-led team of researchers, MVI has been implicated in a new role—interacting with RNA polymerase to drive cellular transcription.
In a number of experiments including protein pull-down assays, FRET, and immunofluorescence, the team finds that MVI protein binds to DNA and key proteins. This association with DNA is self-regulated through a “backfolding” of the MVI protein, which can be relieved by the binding of another protein, NDP52. Furthermore, MVI-NDP52 protein complex also binds RNA polymerase II. This association is critical, as depletion of either NDP52 or MVI also reduces steady-state mRNA levels. Moreover, MVI also directly interacts with nuclear receptors to effectively drive expression of target gene.
The team’s paper, published last week in Nature Communications, concludes that MVI has a potential role as an auxiliary motor to drive transcription, directly influencing cell proliferation and migration.
Dr. Christopher Toseland, the study’s senior author, aims to further investigate how myosins are targeted to specific genes as well as their own regulation, particularly in the context of breast cancer. Understanding the role of Myosin VI would highlight further diagnostic clues for the disease as well as new avenues for treatment.
Image: Staining of myosin VI in human cells. Image courtesy of University of Kent.