The conserved RNA exonuclease Rexo5 is required for 3′ end maturation of 28S rRNA, 5S rRNA, and snoRNAs

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 lower level in somatic metazoan cells, but extremely elevated in male and female germ cells. Rexo5 loss-of-function mutants exhibit increased nucleolar size, genomic instability, and defective ribosome subunit export, and die as second instar larvae. Loss-of-germline expression compromises gonadal growth and meiotic entry during germline development.