LAUSR

Protein arginine methyltransferase 5 (PRMT5) is an enzyme responsible for symmetric arginine methylation, which governs multiple crucial cellular events. PRMT5 expression and activity are dysregulated in many malignancies. PRMT5 dynamically shuttles between the cytosol and nucleus, and different subcellular localizations of PRMT5 imposes distinct cellular functions. However, the biological significance and underlying regulatory mechanism of PRMT5 translocation remain elusive. Herein, we found that PRMT5 acetylation/deacetylation status is a major determinant of its translocation and oncogenic function. PRMT5 acetylation not only drives its cytoplasmic localization but also enhances its methyltransferase activity, promoting cancer cell proliferation. On the other hand, PRMT5 deacetylation translocates PRMT5 into nucleus, to protect cells under the stress condition. Our current findings demonstrate that the acetylation/deacetylation-dependent subcellular localization of PRMT5 is a key regulator of its oncogenic properties. Citation Format: Tam Thuy Lu Vo, Yen Thi Do, Thi Tuyet Mai Pham, So-Jin Shin, Jin Young Kim, Seungmee Lee, Eunyoung Ha, Ji Hae Seo. Acetylation regulates the oncogenic functions of PRMT5 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 328.