Introduction
According to the scientific literature, there is no other option than to increase the global yield efficiency and reduce the yield gap to guarantee future global food security – given that further land increase for agriculture is not an acceptable alternative (EPRS 2019). To realize these agricultural goals a new understanding of the mechanisms underlying plant diseases/immunity and new technological developments in crop protection are required. Recent knowledge suggests that agricultural pests and pathogens can be controlled by exogenous or transgene-mediated supply of double-stranded (ds)RNA targeting essential microbial/pest genes: plants expressing target-specific dsRNAs are more resistant to viroids, viruses, bacteria, fungi, oomycetes, nematodes, and insects (for a topical overview see Cai et al. 2018a; Cai et al. 2019; Liu et al. 2020; Šečić et al. 2021).
The broad applicability of engineered RNA interference (RNAi) techniques is in good agreement with recent findings of small (s)RNA trafficking between interacting organisms. In fact, first hints for natural cross-kingdom RNAi (ckRNAi), and the action of fungal sRNA effectors in plants came from studies on plant (barley) transgene-mediated delivery of dsRNA into the pathogenic powdery mildew fungus (Nowara et al. 2010). Subsequently, exchange of sRNAs between the model plant Arabidopsis thaliana and the pathogenic grey mold fungus Botrytis cinerea was demonstrated (Weiberg et al. 2013); and such sRNA exchange turned out to be bidirectional (Wang 2016, Zhang 2016, Cai 2018b). There is accumulating evidence from other plant-pathogen systems across kingdoms (fungi, oomycetes, bacteria) that similarly ckRNAi may modulate the respective interactions, pointing to conservation of the underlying principle. Thus, understanding the basic mechanisms of ckRNAi in diverse plant-microbe interactions will increase our knowledge in plant-microbe RNA comunication and help to improve the agronomic application of dsRNA. Of note, recent reports have challenged the generalization of the ckRNAi model because not all pathogens/pests seem to be amenable to exogenous RNA (Kogel 2021; Qiao et al. 2021; Šečić and Kogel 2021) or/and lack critical components of an RNAi pathway (Nicolás et al. 2013; Kettles et al. 2018; Šečić and Kogel 2021).
An RNAi-based technology has already been approved by the Canadian Food Inspection Agency in 2016 and the US Environmental Protection Agency in 2017 (Head et al. 2017), indicating its market validity. However, while numerous reports provide proof-of-concept towards RNA applications in crop protection, many questions remain unsolved regarding scientific, regulatory and safety issues (Kookana et al. 2014). Although GMO (genetically modified organism) strategies are already approved, alternative technologies such as direct dsRNA delivery have been suggested and may have a better prognosis for application because of the higher public acceptance of non-GMO techniques. The latter technology has some technical advantages such as flexibility of target selection and high potential for immediate adaptation to emerging pests and diseases. While the exRNA consortium is clearly focused on plant-microbe interactions, it is important not to ignore the knowledge about “pest” control by RNA as it is more advanced and mechanistic aspects, albeit quite different from microbes, are better understood (Figure 1).
