Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Chickens
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Computational Biology / methods
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Lizards
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Male
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Mice
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Mitochondria / genetics*
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Mitochondria / metabolism
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism
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Open Reading Frames
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Pachytene Stage
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Phospholipase D / genetics
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Phospholipase D / metabolism
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Protein Binding
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Protein Biosynthesis
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Proteins / genetics
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Proteins / metabolism
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RNA Helicases / genetics
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RNA Helicases / metabolism
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RNA Precursors / genetics*
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RNA Precursors / metabolism
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RNA, Small Interfering / biosynthesis
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RNA, Small Interfering / genetics*
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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Ribosomes / genetics*
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Ribosomes / metabolism
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Testis / cytology
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Testis / metabolism*
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Voltage-Dependent Anion Channel 1 / genetics
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Voltage-Dependent Anion Channel 1 / metabolism
Substances
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Mitochondrial Proteins
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Proteins
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RNA Precursors
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RNA, Small Interfering
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RNA-Binding Proteins
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Tdrd5 protein, mouse
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Tdrkh protein, mouse
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Vdac1 protein, mouse
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Voltage-Dependent Anion Channel 1
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Phospholipase D
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mitoPLD protein, mouse
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Mov10l1 protein, mouse
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RNA Helicases