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| Status |
Public on May 23, 2023 |
| Title |
Regulatory logic of endogenous RNAi in silencing de novo genomic conflicts |
| Organisms |
Drosophila melanogaster; Drosophila simulans |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
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| Summary |
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 bears compelling signatures of sex chromosome conflict and provides insight into molecular strategies that underlie hpRNA emergence. In particular, our data support the existence of ongoing rapid evolution of Nmy/Dox-related networks, recurrent targeting of testis HMG Box loci by hpRNAs, and connections to transposons. 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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| Overall design |
Comparative analysis of testis transcriptomic data (RNA-seq and small RNA) between wildtype and core RNAi factor mutant dcr2 in two closely related Drosophila species namely, D. melanogaster and D. simulans.
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| Contributor(s) |
Vedanayagam J, Lin C, Papareddy R, Nodine M, Flynt AS, Wen J, Lai EC |
| Citation missing |
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| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| K99 GM137077 |
Selfish meiotic drive and the role of RNAi in defending intragenomic conflict |
Sloan Kettering Institute for Cancer Research |
Jeffrey Vedanayagam |
| R01 HD108914 |
Essential roles for RNAi/hpRNAs to resolve intragenomic conflicts in the male germline |
Sloan Kettering Institute for Cancer Research |
Eric C Lai |
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| Submission date |
Apr 20, 2023 |
| Last update date |
May 26, 2023 |
| Contact name |
Jeffrey Vedanayagam |
| E-mail(s) |
vedanayj@mskcc.org
|
| Organization name |
Sloan-Kettering Institute
|
| Department |
Department of Developmental Biology
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| Lab |
Eric Lai
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| Street address |
1275 York Avenue
|
| City |
New Yor |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (3) |
| GPL17275 |
Illumina HiSeq 2500 (Drosophila melanogaster) |
| GPL22293 |
Illumina HiSeq 2500 (Drosophila simulans) |
| GPL33351 |
Illumina HiSeq 1000 (Drosophila simulans) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA957612 |
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