Publications and Research
Document Type
Article
Publication Date
10-15-2019
Abstract
While nuclear tau plays a role in DNA damage response (DDR) and chromosome relaxation, the mechanisms behind these functions are not fully understood. Here, we show that tau forms complex(es) with factors involved in nuclear mRNA processing such as tumor suppressor p53 and poly(A)-specific ribonuclease (PARN) deadenylase. Tau induces PARN activity in different cellular models during DDR, and this activation is further increased by p53 and inhibited by tau phosphorylation at residues implicated in neurological disorders. Tau’s binding factor Pin1, a mitotic regulator overexpressed in cancer and depleted in Alzheimer’s disease (AD), also plays a role in the activation of nuclear deadenylation. Tau, Pin1 and PARN target the expression of mRNAs deregulated in AD and/or cancer. Our findings identify novel biological roles of tau and toxic effects of hyperphosphorylated-tau. We propose a model in which factors involved in cancer and AD regulate gene expression by interactions with the mRNA processing machinery, affecting the transcriptome and suggesting insights into alternative mechanisms for the initiation and/or developments of these diseases.
Comments
This work was originally published in Frontiers in Molecular Neuroscience available at https://doi.org/10.3389/fnmol.2019.00242
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.