microorganisms Review RNase III, Ribosome Biogenesis and Beyond Maxence Lejars 1, * ,† , Asaki Kobayashi 1,† and Eliane Hajnsdorf 2, *   Citation: Lejars, M.; Kobayashi, A.; Hajnsdorf, E. RNase III, Ribosome Biogenesis and Beyond. Microorganisms 2021, 9, 2608. https://doi.org/10.3390/ microorganisms9122608 Academic Editor: José Marques Andrade Received: 17 November 2021 Accepted: 15 December 2021 Published: 17 December 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan; asaki.lejars@md.tsukuba.ac.jp 2 Institut de Biologie Physico-Chimique, UMR8261, CNRS, Université de Paris, 75005 Paris, France * Correspondence: maxence.lejars@md.tsukuba.ac.jp (M.L.); eliane.hajnsdorf@ibpc.fr (E.H.); Tel.: +81-298533928 (M.L.); +33-158415126 (E.H.) † These authors contributed equally as first authors. Abstract: The ribosome is the universal catalyst for protein synthesis. Despite extensive studies, the diversity of structures and functions of this ribonucleoprotein is yet to be fully understood. Deciphering the biogenesis of the ribosome in a step-by-step manner revealed that this complexity is achieved through a plethora of effectors involved in the maturation and assembly of ribosomal RNAs and proteins. Conserved from bacteria to eukaryotes, double-stranded specific RNase III enzymes play a large role in the regulation of gene expression and the processing of ribosomal RNAs. In this review, we describe the canonical role of RNase III in the biogenesis of the ribosome comparing conserved and unique features from bacteria to eukaryotes. Furthermore, we report additional roles in ribosome biogenesis re-enforcing the importance of RNase III. Keywords: RNase III; ribosome biogenesis; bacteria; eukaryotes 1. Introduction Universally conserved, the ribosome is a complex ribonucleoparticle that acts as the catalyst for protein synthesis. Ribosomal RNAs (rRNAs) and ribosomal proteins are assembled in a stepwise manner involving a plethora of protein and RNA effectors. As one of the most elaborate biological machines, the ribosome remains a major object of study in regard to its complex nature and its heterogeneity in cells [1]. In prokaryotes and eukaryotes, ribosomal biogenesis relies on the transcription of precursors rRNAs, which are processed into mature rRNAs [2,3]. The complexity of the step-by-step process of maturation reveals a need for precision in the timing as well as robustness in the synthesis of rRNAs. In particular, rRNAs adopt complex structures, which are achieved through double-stranded RNA (dsRNA) motifs [4] and which are essential for both catalytic and structural integrity of the mature ribosome [5]. In cells, RNAs are protected by RNA-binding proteins (RBP) and RNA chaperones and are processed by ribonucleases (RNases). Although naked single-stranded RNAs can be cleaved by various RNases, the processing of stable dsRNA structures requires specialized RNase III domain (RIIID)-containing enzymes. RNase IIIs are endoribonucleases cleaving dsRNA conserved from bacteria (e.g., RNase III) to eukaryotes (e.g., Rnt1, Drosha and Dicer) both in terms of structure and function [6–11]. RNase III was first identified for its role in the initial step of rRNA maturation in the model organism Escherichia coli [12]. Subsequent studies demonstrated that RNase III is also involved in the regulation of gene expression in bacteria and the maturation of non-coding RNAs in eukaryotes. In this review, we focus on the diversity of RNase III enzymes from bacteria to eukaryotes and their roles in ribosome assembly. First, we illustrate the diversity in the RNase III family from E. coli RNase III to the more specialized Drosha and Dicer enzymes. We then recapitulate how RNase III enzymes are directly involved in the maturation of rRNAs. Finally, we report other indirect roles of RNase III in ribosome biogenesis, highlighting its importance in ribosome homeostasis. Microorganisms 2021, 9, 2608. https://doi.org/10.3390/microorganisms9122608 https://www.mdpi.com/journal/microorganisms