Molecular Cell
Volume 57, Issue 1, 8 January 2015, Pages 165-178
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Article
Adaptive Regulation of Testis Gene Expression and Control of Male Fertility by the Drosophila Hairpin RNA Pathway

https://doi.org/10.1016/j.molcel.2014.11.025Get rights and content
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Highlights

  • The hpRNA pathway is a testis-directed endo-siRNA pathway in Drosophila

  • hpRNAs have specific regulatory targets and evolve adaptively with them

  • Mutants of hpRNA/RNAi factors exhibit defective spermatogenesis and male subfertility

Summary

Although endogenous siRNAs (endo-siRNAs) have been described in many species, still little is known about their endogenous utility. Here, we show that Drosophila hairpin RNAs (hpRNAs) generate an endo-siRNA class with predominant expression in testes. Although hpRNAs are universally recently evolved, we identify highly complementary protein-coding targets for all hpRNAs. Importantly, we find broad evidence for evolutionary divergences that preferentially maintain compensatory pairing between hpRNAs and targets, serving as first evidence for adaptive selection for siRNA-mediated target regulation in metazoans. We demonstrate organismal impact of hpRNA activity, since knockout of hpRNA1 derepresses its target ATP synthase-β in testes and compromises spermatogenesis and male fertility. Moreover, we reveal surprising male-specific impact of RNAi factors on germ cell development and fertility, consistent with testis-directed function of the hpRNA pathway. Finally, the collected hpRNA loci chronicle an evolutionary timeline that reflects their origins from prospective target genes, mirroring a strategy described for plant miRNAs.

Cited by (0)

5

Present address: Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore

6

Present address: Centro de Biología Molecular CSIC-UAM, Universidad Autónoma de Madrid, 28049 Madrid, Spain

7

Present address: Calico Life Sciences, South San Francisco, CA 94080, USA

8

Co-first Author