RT Journal Article
SR Electronic
T1 Biophysical properties of AKAP95 protein condensates regulate splicing and tumorigenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 536839
DO 10.1101/536839
A1 Wei Li
A1 Jing Hu
A1 Bi Shi
A1 Francesco Palomba
A1 Michelle A. Digman
A1 Enrico Gratton
A1 Hao Jiang
YR 2020
UL http://biorxiv.org/content/early/2020/06/09/536839.abstract
AB It remains unknown if biophysical or material properties of biomolecular condensates regulate cancer. Here we show that AKAP95, a nuclear protein that regulates transcription and RNA splicing, plays an important role in tumorigenesis by supporting cancer cell growth and suppressing oncogene-induced senescence. AKAP95 forms phase-separated and liquid-like condensates in vitro and in nucleus. Mutations of key residues to different amino acids perturb AKAP95 condensation in opposite directions. Importantly, the activity of AKAP95 in splice regulation is abolished by disruption of condensation, significantly impaired by hardening of condensates, and regained by substituting its condensation-mediating region with other condensation-mediating regions from irrelevant proteins. Moreover, the abilities of AKAP95 in regulating gene expression and supporting tumorigenesis require AKAP95 to form condensates with proper liquidity and dynamicity. These results link phase separation to tumorigenesis and uncover an important role of appropriate biophysical properties of protein condensates in gene regulation and cancer.Competing Interest StatementThe authors have declared no competing interest.