The Conserved RNA Exonuclease Rexo5 Is Required for 3′ End Maturation of 28S rRNA, 5S rRNA, and snoRNAs

Abstract

SUMMARY Non-coding RNA biogenesis in higher eukaryotes has not been fully characterized. Here, we studied the Drosophila melanogaster Rexo5 (CG8368) protein, a metazoan-specific member of the DEDDh 3′-5′ single-stranded RNA exonucleases, by genetic, biochemical, and RNA sequencing approaches. Rexo5 is required for small nucleolar RNA (snoRNA) and ribosomal RNA (rRNA) biogenesis, and is essential in D. melanogaster. Loss-of-function mutants accumulate improperly 3′-end-trimmed 28S rRNA, 5S rRNA, and snoRNA precursors in vivo. Rexo5 is ubiquitously expressed at low levels in somatic metazoan cells, but extremely elevated in male and female germ cells. Loss of Rexo5 leads to increased nucleolar size, genomic instability, defective ribosome subunit export and larval death. Loss-of-germline expression compromises gonadal growth and meiotic entry during germline development.

Interspecies analysis of MYC targets identifies tRNA synthetases as mediators of growth and survival in MYC-overexpressing cells

“…For all genes except Myc and rhea, the nucleolar area resulting from knockdown was greater than that in controls. This is likely due to increased ribosomal nucleolar stress, as evidenced by the uneven DAPI and Fibrillarin staining and consistent with a previous report (31). Concurrent knockdown of Myc and the 10 genes with the highest-scoring nucleolar area phenotypes dramatically reduced the area compared with each gene alone ( Fig.…”

Pre-Ribosomal RNA Processing in Human Cells: From Mechanisms to Congenital Diseases

“…La has affinity for uridylates in 3′ and acts as a chaperone. The 5S* RNA 3′ end is processed by a 3′–5′ exonuclease, which was recently identified as REXO5 in Drosophila [35]. This exonuclease is evolutionary conserved, and its human ortholog is located in the nucleolus [35,93], which supports a similar role in human 5S* RNA processing.…”

“…The 5S* RNA 3′ end is processed by a 3′–5′ exonuclease, which was recently identified as REXO5 in Drosophila [35]. This exonuclease is evolutionary conserved, and its human ortholog is located in the nucleolus [35,93], which supports a similar role in human 5S* RNA processing. However, in mouse, Rexo5 is not essential to viability and fertility, and it does not concentrate in the nucleolus [93].…”

“…The 5S rRNA (121 nt) is transcribed by RNA polymerase III from repeated gene copies located on chromosome 1. As little is known about the maturation of 5S precursors in humans (depicted in orange) [34], data recently obtained in Drosophila were used [35]. When identified, endoribonucleases are quoted in black, and 5′-3′ or 3′-5′ exoribonucleases in grey.…”

Generation of 2′,3′-Cyclic Phosphate-Containing RNAs as a Hidden Layer of the Transcriptome

“…rRNA maturation requires a cP-forming endoribonuclease, Lethal in the absence of Ssd1 (Las1 in yeast; Las1L in human) ( Castle et al, 2010 ; Schillewaert et al, 2012 ). In yeast, rRNA maturation starts from processing of a nascent 37S rRNA precursor into shorter precursors, including 27S rRNA ( Henras et al, 2015 ; Gerstberger et al, 2017 ). The 27S rRNA is further cleaved by Las1 between 5.8S and 25S rRNA sequences, generating 7S rRNA as a 5′-cleavage product with a cP ( Gasse et al, 2015 ; Pillon et al, 2017 ).…”