PT  - JOURNAL ARTICLE
AU  - Chakrapani, Baskar
AU  - Khan, Mohd Imran K
AU  - Kadumuri, Rajashekar Varma
AU  - Gupta, Somlee
AU  - Verma, Mamta
AU  - Awasthi, Sharad
AU  - Govindaraju, Gayathri
AU  - Mahesh, Arun
AU  - Rajavelu, Arumugam
AU  - Chavali, Sreenivas
AU  - Dhayalan, Arunkumar
TI  - The uncharacterized protein FAM47E interacts with PRMT5 and regulates its functions
AID  - 10.26508/lsa.202000699
DP  - 2021 Mar 01
TA  - Life Science Alliance
PG  - e202000699
VI  - 4
IP  - 3
4099  - http://www.life-science-alliance.org/content/4/3/e202000699.short
4100  - http://www.life-science-alliance.org/content/4/3/e202000699.full
SO  - Life Sci. Alliance2021 Mar 01; 4
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.