RT Journal Article
SR Electronic
T1 The uncharacterized protein FAM47E interacts with PRMT5 and regulates its functions
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000699
DO 10.26508/lsa.202000699
VO 4
IS 3
A1 Baskar Chakrapani
A1 Mohd Imran K Khan
A1 Rajashekar Varma Kadumuri
A1 Somlee Gupta
A1 Mamta Verma
A1 Sharad Awasthi
A1 Gayathri Govindaraju
A1 Arun Mahesh
A1 Arumugam Rajavelu
A1 Sreenivas Chavali
A1 Arunkumar Dhayalan
YR 2021
UL https://www.life-science-alliance.org/content/4/3/e202000699.abstract
AB Protein arginine methyltransferase 5 (PRMT5) symmetrically dimethylates arginine residues in various proteins affecting diverse cellular processes such as transcriptional regulation, splicing, DNA repair, differentiation, and cell cycle. Elevated levels of PRMT5 are observed in several types of cancers and are associated with poor clinical outcomes, making PRMT5 an important diagnostic marker and/or therapeutic target for cancers. Here, using yeast two-hybrid screening, followed by immunoprecipitation and pull-down assays, we identify a previously uncharacterized protein, FAM47E, as an interaction partner of PRMT5. We report that FAM47E regulates steady-state levels of PRMT5 by affecting its stability through inhibition of its proteasomal degradation. Importantly, FAM47E enhances the chromatin association and histone methylation activity of PRMT5. The PRMT5–FAM47E interaction affects the regulation of PRMT5 target genes expression and colony-forming capacity of the cells. Taken together, we identify FAM47E as a protein regulator of PRMT5, which promotes the functions of this versatile enzyme. These findings imply that disruption of PRMT5–FAM47E interaction by small molecules might be an alternative strategy to attenuate the oncogenic function(s) of PRMT5.