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Regulatory logic of endogenous RNAi in silencing de novo genomic conflicts

Although the biological utilities of endogenous RNAi (endo-RNAi) have been largely elusive, recent studies reveal its critical role in the non-model fruitfly Drosophila simulans to suppress selfish genes, whose unchecked activities can severely impair spermatogenesis. In particular, hairpin RNA (hpR...

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Autores principales: Vedanayagam, Jeffrey, Lin, Ching-Jung, Papareddy, Ranjith, Nodine, Michael, Flynt, Alex S., Wen, Jiayu, Lai, Eric C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317233/
https://www.ncbi.nlm.nih.gov/pubmed/37343034
http://dx.doi.org/10.1371/journal.pgen.1010787
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author Vedanayagam, Jeffrey
Lin, Ching-Jung
Papareddy, Ranjith
Nodine, Michael
Flynt, Alex S.
Wen, Jiayu
Lai, Eric C.
author_facet Vedanayagam, Jeffrey
Lin, Ching-Jung
Papareddy, Ranjith
Nodine, Michael
Flynt, Alex S.
Wen, Jiayu
Lai, Eric C.
author_sort Vedanayagam, Jeffrey
collection PubMed
description Although the biological utilities of endogenous RNAi (endo-RNAi) have been largely elusive, recent studies reveal its critical role in the non-model fruitfly Drosophila simulans to suppress selfish genes, whose unchecked activities can severely impair spermatogenesis. In particular, hairpin RNA (hpRNA) loci generate endo-siRNAs that suppress evolutionary novel, X-linked, meiotic drive loci. The consequences of deleting even a single hpRNA (Nmy) in males are profound, as such individuals are nearly incapable of siring male progeny. Here, comparative genomic analyses of D. simulans and D. melanogaster mutants of the core RNAi factor dcr-2 reveal a substantially expanded network of recently-emerged hpRNA-target interactions in the former species. The de novo hpRNA regulatory network in D. simulans provides insight into molecular strategies that underlie hpRNA emergence and their potential roles in sex chromosome conflict. In particular, our data support the existence of ongoing rapid evolution of Nmy/Dox-related networks, and recurrent targeting of testis HMG-box loci by hpRNAs. Importantly, the impact of the endo-RNAi network on gene expression flips the convention for regulatory networks, since we observe strong derepression of targets of the youngest hpRNAs, but only mild effects on the targets of the oldest hpRNAs. These data suggest that endo-RNAi are especially critical during incipient stages of intrinsic sex chromosome conflicts, and that continual cycles of distortion and resolution may contribute to speciation.
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spelling pubmed-103172332023-07-04 Regulatory logic of endogenous RNAi in silencing de novo genomic conflicts Vedanayagam, Jeffrey Lin, Ching-Jung Papareddy, Ranjith Nodine, Michael Flynt, Alex S. Wen, Jiayu Lai, Eric C. PLoS Genet Research Article Although the biological utilities of endogenous RNAi (endo-RNAi) have been largely elusive, recent studies reveal its critical role in the non-model fruitfly Drosophila simulans to suppress selfish genes, whose unchecked activities can severely impair spermatogenesis. In particular, hairpin RNA (hpRNA) loci generate endo-siRNAs that suppress evolutionary novel, X-linked, meiotic drive loci. The consequences of deleting even a single hpRNA (Nmy) in males are profound, as such individuals are nearly incapable of siring male progeny. Here, comparative genomic analyses of D. simulans and D. melanogaster mutants of the core RNAi factor dcr-2 reveal a substantially expanded network of recently-emerged hpRNA-target interactions in the former species. The de novo hpRNA regulatory network in D. simulans provides insight into molecular strategies that underlie hpRNA emergence and their potential roles in sex chromosome conflict. In particular, our data support the existence of ongoing rapid evolution of Nmy/Dox-related networks, and recurrent targeting of testis HMG-box loci by hpRNAs. Importantly, the impact of the endo-RNAi network on gene expression flips the convention for regulatory networks, since we observe strong derepression of targets of the youngest hpRNAs, but only mild effects on the targets of the oldest hpRNAs. These data suggest that endo-RNAi are especially critical during incipient stages of intrinsic sex chromosome conflicts, and that continual cycles of distortion and resolution may contribute to speciation. Public Library of Science 2023-06-21 /pmc/articles/PMC10317233/ /pubmed/37343034 http://dx.doi.org/10.1371/journal.pgen.1010787 Text en © 2023 Vedanayagam et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Vedanayagam, Jeffrey
Lin, Ching-Jung
Papareddy, Ranjith
Nodine, Michael
Flynt, Alex S.
Wen, Jiayu
Lai, Eric C.
Regulatory logic of endogenous RNAi in silencing de novo genomic conflicts
title Regulatory logic of endogenous RNAi in silencing de novo genomic conflicts
title_full Regulatory logic of endogenous RNAi in silencing de novo genomic conflicts
title_fullStr Regulatory logic of endogenous RNAi in silencing de novo genomic conflicts
title_full_unstemmed Regulatory logic of endogenous RNAi in silencing de novo genomic conflicts
title_short Regulatory logic of endogenous RNAi in silencing de novo genomic conflicts
title_sort regulatory logic of endogenous rnai in silencing de novo genomic conflicts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317233/
https://www.ncbi.nlm.nih.gov/pubmed/37343034
http://dx.doi.org/10.1371/journal.pgen.1010787
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