Abstract 4146: USP36 associates with the rixosome complex and promotes ribosome biogenesis

Abstract Eukaryotic ribosome biogenesis is a highly regulated multistep process to generate the ribosome, including transcription of pre-ribosomal RNA (pre-rRNA), rRNA processing, ribosome subunit assembly and export. Dysregulation of ribosome biogenesis has been associated with development of various diseases, including ribosomopathies and cancer. Therefore, it is crucial to understand how ribosome biogenesis is regulated during normal cell homeostasis and how it is deregulated in human diseases. We previously reported that the ubiquitin-specific protease USP36 acts as a SUMO ligase to promote nucleolar protein SUMOylation. Using affinity purification, we found that USP36 associates with a number of nucleolar and ribosome biogenesis-related proteins, including the rixosome complex that consists of Las1L, Nol9, MDN1, Pelp1, WDR36, Tex10 and SENP3 and plays a critical function in ribosome maturation. We confirmed that that USP36 interacts with all the components of the rixosome complex. We further showed that USP36 promotes the SUMOylation of Las1L, Nol9 and Pelp1, suggesting that USP36 promotes rixosome protein group SUMOylation. As USP36 is a ubiquitin specific protease, we also test whether the stability of these rixosome proteins is regulated by USP36. We found that the levels of MDN1 and Las1L, Nol9 are reduced upon USP36 knockdown. Abolishing Las1L SUMOylation impaired rRNA processing and inhibited cell growth. Together, these results suggest that USP36 plays an important role in regulating ribosome biogenesis by post-translationally regulating the function of rixosome complex. Citation Format: Yanping Li, Xiao-Xin Sun, Mushui Dai. USP36 associates with the rixosome complex and promotes ribosome biogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4146.