Unraveling the biogenesis of a novel class of viral small RNAs

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In a recent publication in Nucleic Acids Research, Pascal Miesen and Erika Girardi in the group of Ronald van Rij, Dept. Medical Microbiology characterize the molecular mechanisms underlying the biogenesis of viral piRNAs in vector mosquitoes.

Arthropod-borne viruses (arboviruses) such as Dengue virus, Chikungunya virus or Sindbis virus are transmitted between vertebrate hosts by mosquito vectors, which carry these viruses without any apparent loss of fitness. Virus replication in these insects is controlled by the RNA interference machinery with at its core small interfering RNAs (siRNAs). The unexpected finding of virus-derived PIWI-interacting RNAs (piRNAs) in Aedes mosquitoes indicates that yet another small RNA silencing pathway targets viruses in these animals. Initially, the piRNA pathway was only implicated in transposon silencing in model organisms including mice and fruit flies. Yet, the discovery of viral piRNAs suggests that it has gained additional functions in mosquitoes. In line with this idea, the PIWI gene family is expanded in these insects, but the contribution of the individual PIWI proteins to viral and transposon piRNA biogenesis is not understood. Miesen and colleagues now identify Piwi5 and Ago3 as the first biogenesis factors for viral piRNAs. The authors show that the production of virus-derived piRNAs is almost exclusively dependent on Piwi5 and Ago3, whereas the biogenesis of transposon-derived piRNAs is more versatile and involves additional PIWI proteins. The authors therefore propose that specialized arms of the mosquito piRNA pathway recognize and produce piRNAs from endogenous or exogenous parasitic RNAs.

Distinct sets of PIWI proteins produce arbovirus and transposon-derived piRNAs in Aedes aegypti mosquito cells. Nucleic Acids Res. 2015 

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