Hierarchical length and sequence preferences establish a single major piRNA 3′-end

Hierarchical length and sequence preferences establish a single major piRNA 3′-end

PIWI-interacting RNAs (piRNAs) guard germline genomes against the deleterious action of mobile genetic elements. PiRNAs use extensive base-pairing to recognize their targets and variable 3′ends could change the specificity and efficacy of piRNA silencing. Here, we identify conserved rules that ensur...

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Bibliographic Details
Published in:iScience 2022-06, Vol.25 (6), p.104427-104427, Article 104427
Main Authors: Stoyko, Daniel, Genzor, Pavol, Haase, Astrid D.
Format: Article
Language:eng
Subjects:
Biological sciences
Cell biology
Molecular biology
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Summary:PIWI-interacting RNAs (piRNAs) guard germline genomes against the deleterious action of mobile genetic elements. PiRNAs use extensive base-pairing to recognize their targets and variable 3′ends could change the specificity and efficacy of piRNA silencing. Here, we identify conserved rules that ensure the generation of a single major piRNA 3′end in flies and mice. Our data suggest that the PIWI proteins initially define a short interval on pre-piRNAs that grants access to the ZUC-processor complex. Within this Goldilocks zone, the preference to cut in front of Uridine determines the ultimate processing site. We observe a mouse-specific roadblock that relocates the Goldilocks zone and generates an opportunity for consecutive trimming. Our data reveal a conserved hierarchy between length and sequence preferences that controls the piRNA sequence space. The unanticipated precision of 3′end formation bolsters the emerging understanding that the functional piRNA sequence space is tightly controlled to ensure effective defense. [Display omitted] •Every piRNA has a single major 3′end•Length preference trumps sequence preference during 3′end formation•A hierarchy of length and sequence preferences is conserved in flies and mice•Relocation of the Goldilocks zone generates opportunity for trimming in mice Biological sciences; Cell biology; Molecular biology
ISSN:2589-0042
2589-0042