Processing of the ribosomal ubiquitin-like fusion protein FUBI-eS30/FAU is required for 40S maturation and depends on USP36

eLife

Emanuel Wyler¹  Ulrike Kutay¹  Caroline Ashiono¹  Ludovic C Gillet¹  Ivo Zemp¹  Kerstin Dörner²  Jasmin van den Heuvel² 

[1] Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland;Institute of Biochemistry, Department of Biology, ETH Zurich, Zurich, Switzerland;Molecular Life Sciences Ph.D. Program, Zurich, Switzerland;

关键词: ubiquitin;    ribosome biogenesis;    DUB;    FUBI;    translation;    nucleolus;    Human;   

DOI  :  10.7554/eLife.70560

来源: eLife Sciences Publications, Ltd

【 摘 要 】

In humans and other holozoan organisms, the ribosomal protein eS30 is synthesized as a fusion protein with the ubiquitin-like protein FUBI. However, FUBI is not part of the mature 40S ribosomal subunit and cleaved off by an as-of-yet unidentified protease. How FUBI-eS30 processing is coordinated with 40S subunit maturation is unknown. To study the mechanism and importance of FUBI-eS30 processing, we expressed non-cleavable mutants in human cells, which affected late steps of cytoplasmic 40S maturation, including the maturation of 18S rRNA and recycling of late-acting ribosome biogenesis factors. Differential affinity purification of wild-type and non-cleavable FUBI-eS30 mutants identified the deubiquitinase USP36 as a candidate FUBI-eS30 processing enzyme. Depletion of USP36 by RNAi or CRISPRi indeed impaired FUBI-eS30 processing and moreover, purified USP36 cut FUBI-eS30 in vitro. Together, these data demonstrate the functional importance of FUBI-eS30 cleavage and identify USP36 as a novel protease involved in this process.

【 授权许可】

CC BY