Leaning Into the Bite: The piRNA Pathway as an Exemplar for the Genetic Engineering Need in Mosquitoes.

Vanessa M Macias,Mariangela Bonizzoni,Jason L Rasgon,Umberto Palatini

doi:10.3389/fcimb.2020.614342

Vanessa M Macias, Mariangela Bonizzoni + Show 2 more

Open Access

https://doi.org/10.3389/fcimb.2020.614342

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Abstract

The piRNA pathway is a specialized small RNA interference that in mosquitoes is mechanistically distant from analogous biology in the Drosophila model. Current genetic engineering methods, such as targeted genome manipulation, have a high potential to tease out the functional complexity of this intricate molecular pathway. However, progress in utilizing these methods in arthropod vectors has been geared mostly toward the development of new vector control strategies rather than to study cellular functions. Herein we propose that genetic engineering methods will be essential to uncover the full functionality of PIWI/piRNA biology in mosquitoes and that extending the applications of genetic engineering on other aspects of mosquito biology will grant access to a much larger pool of knowledge in disease vectors that is just out of reach. We discuss motivations for and impediments to expanding the utility of genetic engineering to study the underlying biology and disease transmission and describe specific areas where efforts can be placed to achieve the full potential for genetic engineering in basic biology in mosquito vectors. Such efforts will generate a refreshed intellectual source of novel approaches to disease control and strong support for the effective use of approaches currently in development.

Highlights

The piRNA pathway (PIWI-interacting RNA pathway) is a fascinating biological system that allows an organism to identify parasitic nucleic acids in its cells and create a heritable, genetic memory of these exogenous sequences (Figures 1A–D, Siomi et al, 2011)
The activity against a specific target can be amplified by ping-pong amplification, where-by additional piRNAs are generated by interaction with the target RNA and PIWI paralogs (Brennecke et al, 2007; Czech and Hannon, 2016)
Complexity of function within an organism is added by protein binding partners that interact with the PIWI/ piRNA complex and direct or influence its localization and activity (Brower-Toland et al, 2007; Czech and Hannon, 2011; Arkov, 2018)

Summary

Introduction

The piRNA pathway (PIWI-interacting RNA pathway) is a fascinating biological system that allows an organism to identify parasitic nucleic acids in its cells and create a heritable, genetic memory of these exogenous sequences (Figures 1A–D, Siomi et al, 2011). Knowing that this biology targets foreign and integrated mobile DNA elements, is it possible that genetically modified mosquitoes could recognize transgenes, such as those being developed and deployed for public health efforts to mitigate mosquito-borne diseases?

Results

Conclusion