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ea0090rc5.4 | Rapid Communications 5: Adrenal and Cardiovascular Endocrinology 1 | ECE2023

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is likely a genome instability disease due to ARMC5’s role in resolving transcription-replication conflict

Lao Linjiang , Bourdeau Isabelle , Gagliardi Lucia , He Xiao , Torpy David , Scott Hamish , Lacroix Andre , Luo Hongyu , Wu Jiangping

ARMC5 mutations are associated with PBMAH risks, but the ARMC5 action mechanism remains unknown. We discovered that ARMC5 was part of a novel ubiquitin ligase (E3) specific for RPB1, the largest Pol II subunit. ARMC5 deletion significantly reduced RPB1 ubiquitination and increased RPB1 accumulation. Surprisingly, the degradation of not only RPB1 but all the 12 subunits of Pol II was compromised in the absence of ARMC5, suggesting that this E3 acts on RPB1 and molecules in its ...