Ribosomes guide pachytene piRNA formation on long intergenic piRNA precursors

• Published in: Nature cell biology Vol. 22; no. 2; pp. 200 - 212
• Main Authors: Sun, Yu H., Zhu, Jiang, Xie, Li Huitong, Li, Ziwei, Meduri, Rajyalakshmi, Zhu, Xiaopeng, Song, Chi, Chen, Chen, Ricci, Emiliano P., Weng, Zhiping, Li, Xin Zhiguo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2020; Nature Publishing Group
• Subjects: 14; 14/63; 38; 38/39; 38/90; 45; 631/136/2434/1822; 631/45/500; 64; 64/60; 82; 82/80; Animals; Biology; Biomedical and Life Sciences; Biosynthesis; Cancer Research; Cell Biology; Chickens; Computational Biology - methods; Developmental Biology; DNA helicase; Fertility; Genomes; Life Sciences; Lizards; Male; Mice; Mitochondria; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Non-coding RNA; Open Reading Frames; Pachytene; Pachytene Stage; Phospholipase D - genetics; Phospholipase D - metabolism; Precursors; Protein Binding; Protein Biosynthesis; Proteins; Proteins - genetics; Proteins - metabolism; Reproductive Biology; Ribosomes; Ribosomes - genetics; Ribosomes - metabolism; RNA; RNA helicase; RNA Helicases - genetics; RNA Helicases - metabolism; RNA polymerase; RNA Precursors - genetics; RNA Precursors - metabolism; RNA, Small Interfering - biosynthesis; RNA, Small Interfering - genetics; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Sexual reproduction; Spermatogenesis; Stem Cells; Sucrose; Testes; Testis - cytology; Testis - metabolism; Translocation; Voltage-Dependent Anion Channel 1 - genetics; Voltage-Dependent Anion Channel 1 - metabolism; Canada; non-coding RNA; PIWI-interacting RNA; piRNA; translation; uORF; ribosome; short open reading frame; testis; germ cell; PIWI-interacting RNA piRNA ribosome translation testis germ cell non-coding RNA reproduction short open reading frame uORF; reproduction
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/s41556-019-0457-4

PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs essential for fertility. In adult mouse testes, most piRNAs are derived from long single-stranded RNAs lacking annotated open reading frames (ORFs). The mechanisms underlying how piRNA sequences are defined during the cleavages of piRNA precursors remain elusive. Here, we show that 80S ribosomes translate the 5′-proximal short ORFs (uORFs) of piRNA precursors. The MOV10L1/Armitage RNA helicase then facilitates the translocation of ribosomes into the uORF downstream regions (UDRs). The ribosome-bound UDRs are targeted by piRNA processing machinery, with the processed ribosome-protected regions becoming piRNAs. The dual modes of interaction between ribosomes and piRNA precursors underlie the distinct piRNA biogenesis requirements at uORFs and UDRs. Ribosomes also mediate piRNA processing in roosters and green lizards, implying that this mechanism is evolutionarily conserved in amniotes. Our results uncover a function for ribosomes on non-coding regions of RNAs and reveal the mechanisms underlying how piRNAs are defined. Sun et al. uncover a conserved mechanism by which ribosomes function in defining the position of pachytene piRNA formation on long single-stranded RNAs during spermatogenesis.