Kim KT
Pohang University of Science and Technology, South Korea
Title: VRK2 mRNA stability and polyQ-huntingtin aggregation
Biography
Biography: Kim KT
Abstract
Misfolded proteins with abnormal polyglutamine (polyQ) expansion cause neurodegenerative disorders, including
Huntington's disease (HD). Recently, it was found that polyQ aggregates accumulate due to vaccinia-related kinase 2
(VRK2)-mediated degradation of TCP-1 ring complex (TRiC)/chaperonin-containing TCP-1 (CCT), which has an essential
role in the prevention of polyQ protein aggregation and cytotoxicity. The levels of VRK2 are known to be much higher in
actively proliferating cells but are maintained at a low level in the brain via an unknown mechanism. Here, we found that basal
levels of neuronal cell-specific VRK2 mRNA are maintained by post-transcriptional, rather than transcriptional, regulation.
Moreover, heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) specifically binds to the 3ʹUTR of VRK2 mRNA in
neuronal cells to reduce the mRNA stability. As a result, we found a dramatic decrease in CCT4 protein levels in response to a
reduction in hnRNP Q levels, which was followed by an increase in polyQ aggregation. Taken together, these results provide
new insights into how neuronal hnRNP Q decreases VRK2 mRNA stability and contribute to the prevention of HD, while also
identifying new prognostic markers of HD.