Ribonuclease inhibitor and angiogenin system regulates cell type-specific global translation.

Stillinovic, Martina; Sarangdhar, Mayuresh Anant; Andina, Nicola; Tardivel, Aubry; Greub, Frédéric; Bombaci, Giuseppe; Ansermet, Camille; Zatti, Marco; Saha, Dipanjali; Xiong, Jieyu; Sagae, Takeru; Yokogawa, Mariko; Osawa, Masanori; Heller, Manfred; Keogh, Adrian; Keller, Irene; Angelillo-Scherrer, Anne; Allam, Ramanjaneyulu (2024). Ribonuclease inhibitor and angiogenin system regulates cell type-specific global translation. Science Advances, 10(22) American Association for the Advancement of Science 10.1126/sciadv.adl0320

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Translation of mRNAs is a fundamental process that occurs in all cell types of multicellular organisms. Conventionally, it has been considered a default step in gene expression, lacking specific regulation. However, recent studies have documented that certain mRNAs exhibit cell type-specific translation. Despite this, it remains unclear whether global translation is controlled in a cell type-specific manner. By using human cell lines and mouse models, we found that deletion of the ribosome-associated protein ribonuclease inhibitor 1 (RNH1) decreases global translation selectively in hematopoietic-origin cells but not in the non-hematopoietic-origin cells. RNH1-mediated cell type-specific translation is mechanistically linked to angiogenin-induced ribosomal biogenesis. Collectively, this study unravels the existence of cell type-specific global translation regulators and highlights the complex translation regulation in vertebrates.

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