PT - JOURNAL ARTICLE AU - Eline Hendrix AU - Regina Andrijes AU - Uncaar Boora AU - Arashpreet Kaur AU - James R Bundred AU - Adam Zayer AU - Raphael Heilig AU - Christian A E Westrip AU - Sally C Fletcher AU - Charlotte D Eaton AU - Tristan J Kennedy AU - Sonia Piasecka AU - Roman Fischer AU - Stephen J Smerdon AU - Mathew L Coleman TI - A protein hydroxylase couples epithelial membrane biology to nucleolar ribosome biogenesis AID - 10.1101/2023.03.15.532818 DP - 2023 Jan 01 TA - bioRxiv PG - 2023.03.15.532818 4099 - http://biorxiv.org/content/early/2023/03/16/2023.03.15.532818.short 4100 - http://biorxiv.org/content/early/2023/03/16/2023.03.15.532818.full AB - Jumonji-C (JmjC) ribosomal protein hydroxylases are an ancient class of oxygen- and Fe(II)-dependent oxygenases that spawned the wider JmjC family and Histone Lysine Demethylases (KDMs) in eukaryotes. Myc-induced Antigen (MINA) has been implicated in ribosome biogenesis and was assigned as a nucleolar-localized JmjC histidyl hydroxylase of the large ribosomal subunit protein RPL27A, consistent with reports that it supports cell growth and viability in a variety of tumor cell types. Reported roles in diverse aspects of disease biology may be consistent with additional MINA functions, although the molecular mechanisms involved remain unclear. Here, we describe an extra-nucleolar interaction of MINA with the Hinge domain of the membrane-associated guanylate kinase, MPP6. We show that MINA promotes the expression and membrane localization of MPP6 and that the MINA-MPP6 pathway is required for epithelial tight junction integrity and barrier function. The function of MINA in this novel pathway is suppressed by ribosomal RNA transcription and the nucleolar MINA interactome, which sequesters MINA in the nucleoli of growing cells. Our work sheds light on how quiescent cells lose adhesion as they switch to proliferate states associated with increased ribosome biogenesis.Competing Interest StatementThe authors have declared no competing interest.