PT  - JOURNAL ARTICLE
AU  - Natalia Pinzón
AU  - Stéphanie Bertrand
AU  - Lucie Subirana
AU  - Isabelle Busseau
AU  - Hector Escrivá
AU  - Hervé Seitz
TI  - Functional lability of RNA-dependent RNA polymerases in animals
AID  - 10.1101/339820
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 339820
4099  - http://biorxiv.org/content/early/2018/09/17/339820.short
4100  - http://biorxiv.org/content/early/2018/09/17/339820.full
AB  - RNA interference (RNAi) requires RNA-dependent RNA polymerases (RdRPs) in many eukaryotes, and RNAi amplification constitutes the only known function for eukaryotic RdRPs. Yet in animals, classical model organisms can elicit RNAi without possessing RdRPs, and only nematode RNAi was shown to require RdRPs. Here we show that RdRP genes are much more common in animals than previously thought, even in insects, where they had been assumed not to exist. RdRP genes were present in the ancestors of numerous clades, and they were subsequently lost at a high frequency. In order to probe the function of RdRPs in a deuterostome (the cephalochordate Branchiostoma lanceolatum), we performed high-throughput analyses of small RNAs from various Branchiostoma developmental stages. Our results show that Branchiostoma RdRPs are active, generating antisense RNAs from spliced RNA templates, yet they do not appear to participate in RNAi: we did not detect any candidate small RNA population exhibiting classical siRNA length or sequence features. Our results show that RdRPs have been independently lost in dozens of animal clades, and even in a clade where they have been conserved (cephalochordates) their function in RNAi amplification is not preserved. Such a dramatic functional variability reveals an unexpected plasticity in RNA silencing pathways.Author summary RNA interference (RNAi) is a conserved gene regulation system in eukaryotes. In non-animal eu-karyotes, it necessitates RNA-dependent RNA polymerases (”RdRPs”). Among animals, only nematodes appear to require RdRPs for RNAi. Yet additional animal clades have RdRPs and it is assumed that they participate in RNAi. Here, we find that RdRPs are much more common in animals than previously thought, but their genes were independently lost in many lineages. Focusing on a species with functional RdRPs (a cephalochordate), we found that it does not use them for RNAi. While RNAi is the only known function for eukaryotic RdRPs, our results suggest additional roles. Eukaryotic RdRPs thus have a complex evolutionary history in animals, with frequent independent losses and apparent functional diversification.