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Nat Commun. 2020 Jan 9;11(1):156. doi: 10.1038/s41467-019-13990-w.

Identification of distinct maturation steps involved in human 40S ribosomal subunit biosynthesis.

Author information

1
Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Campus Unamuno, 37007, Salamanca, Spain.
2
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Campus Unamuno, 37007, Salamanca, Spain.
3
Department of Cell Biology and Neuroscience, Rowan University School of Osteopathic Medicine, Stratford, NJ, 08084, USA.
4
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca, Campus Unamuno, 37007, Salamanca, Spain.
5
Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Campus Unamuno, 37007, Salamanca, Spain. mdosil@usal.es.
6
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Campus Unamuno, 37007, Salamanca, Spain. mdosil@usal.es.
7
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca, Campus Unamuno, 37007, Salamanca, Spain. mdosil@usal.es.
8
Departamento de Bioquímica y Biología Molecular, University of Salamanca, Campus Unamuno, 37007, Salamanca, Spain. mdosil@usal.es.

Abstract

Technical problems intrinsic to the purification of preribosome intermediates have limited our understanding of ribosome biosynthesis in humans. Addressing this issue is important given the implication of this biological process in human disease. Here we report a preribosome purification and tagging strategy that overcomes some of the existing technical difficulties. Using these tools, we find that the pre-40S precursors go through two distinct maturation phases inside the nucleolus and follow a regulatory step that precedes late maturation in the cytoplasm. This regulatory step entails the intertwined actions of both PARN (a metazoan-specific ribonuclease) and RRP12 (a phylogenetically conserved 40S biogenesis factor that has acquired additional functional features in higher eukaryotes). Together, these results demonstrate the usefulness of this purification method for the dissection of ribosome biogenesis in human cells. They also identify distinct maturation stages and metazoan-specific regulatory mechanisms involved in the generation of the human 40S ribosomal subunit.

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