C. elegans “reads” bacterial non-coding RNAs to learn pathogenic avoidance

Abstract

C. elegans is exposed to many different bacteria in its environment, and must distinguish pathogenic from nutritious bacterial food sources. Here, we show that a single exposure to purified small RNAs isolated from pathogenic Pseudomonas aeruginosa (PA14) is sufficient to induce pathogen avoidance, both in the treated animals and in four subsequent generations of progeny. The RNA interference and piRNA pathways, the germline, and the ASI neuron are required for bacterial small RNA-induced avoidance behavior and transgenerational inheritance. A single non-coding RNA, P11, is both necessary and sufficient to convey learned avoidance of PA14, and its C. elegans target, maco-1, is required for avoidance. A natural microbiome Pseudomonas isolate, GRb0427, can induce avoidance via its small RNAs, and the wild C. elegans strain JU1580 responds similarly to bacterial sRNA. Our results suggest that this ncRNA-dependent mechanism evolved to survey the worm's microbial environment, use this information to make appropriate behavioral decisions, and pass this information on to its progeny.

Stress resets ancestral heritable small RNA responses

“…Nuclear small RNAs promote modification of chromatin, and some changes in histone marks are transgenerationally inherited, also in response to environmental changes (Klosin et al, 2017). The worm's small RNA pools can change transgenerationally in response to multiple environmental challenges such as viral and bacterial infection (Kaletsky et al, 2020;Moore et al, 2019;Rechavi et al, 2011), starvation (Ewe et al, 2020;Rechavi et al, 2014), and stressful temperatures (Ni et al, 2016;Schott et al, 2014). Further, C. elegans actively regulates small RNA inheritance and controls the duration and potency of the transgenerational effects across generations (Houri-Ze'evi et al, 2016;Houri-Zeevi and Rechavi, 2017).…”

SID-2 negatively regulates development likely independent of nutritional dsRNA uptake

“…Potentially, the resulting smallRNA fingerprint could serve as an RNA-based memory and by an unknown mechanism be associated with an environmental condition to inform future decision making. Such a mechanism could be involved in the ability of C. elegans to develop aversion to natural and artificial bacterial stressors [ 74 , 75 ]. This hypothesis could be tested with an associated learning assay using dsRNA and sid-2 mutants.…”

Remembering your enemies: mechanisms of within‐generation and multigenerational immune priming in Caenorhabditis elegans

“…2B) [66]. Avoidance is mechanistically different A B C D from CREB-dependent memory and is elicited by bacterial-derived small RNAs [67]. Here, the noncoding RNA P11, expressed only in virulent Pseudomonas, is thought to be taken up by the intestinal SID-2 dsRNA transporter, spread between cells by SID-1 and processed into siRNAs by DCR-1.…”

“…Most research on immune memory in C. elegans has been carried out using human pathogens. C. elegans coexist in nature with a large diversity of bacterial species, and these microbes are likely to induce evolutionarily relevant responses [11,67,75,76]. In addition to bacteria, there are common natural fungal pathogens of C. elegans such as Drechmeria coniospora and a variety of microsporidia species [10,78].…”