Pro- and anti-viral roles of RNA uridylation in plants – URIVir

The general objective of the URIVir project is to understand the biological impact of RNA uridylation on the pathogenicity of phytoviruses. RNA uridylation, the 3’ tailing of RNAs with uridines, is a regulatory post-transcriptional modification, conserved across most eukaryotes. RNA uridylation plays key roles in gene expression, from promoting the maturation of major non-coding RNAs to favoring the degradation of a plethora of other ones, including small RNAs. Uridylation can also tag mRNAs to trigger both 5’-3’ and 3’-5’ degradation. In fact, the full extent of the roles played by RNA uridylation is still being explored and, of note in the context of the URIVir project, RNA uridylation is emerging as a modulator of viral infection. The uridylation of viral RNAs has been reported recently in several organisms including plants and animals. To date, mechanistic insights on the roles of RNA uridylation in host-virus interactions remain fragmentary, with a single recent study revealing a negative impact of RNA uridylation on infection of Caenorhabditis elegans by the Orsay virus and on infection of mammalian cells by the influenza virus. Importantly, detailed mechanistic information and biological insights of the roles of RNA uridylation remain unexplored for plant viruses. The URIVir project is specifically designed to address this question.
In URIVir, RNA uridylation patterns for a range of model and economically relevant plant viruses will be investigated by high-throughput sequencing methods. This analysis will determine the evolutionary conservation of RNA uridylation among the major families of (+)ssRNA phytoviruses. We will identify factors involved in viral RNA uridylation and define how this RNA modification modulates the pathogenicity of selected plant viruses and participates in plant defence against viruses.
URIVir will benefit from complementary expertise of two partners: Partner1 (P1) regroups experts in RNA uridylation, RNA degradation and plant virology, and Partner2 (P2) is a leading team in the study of grapevine fanleaf virus (GFLV). GFLV is the main causal agent of grapevine fanleaf degeneration disease, responsible for drastic yield losses worldwide.
The URIVir project is grounded on key preliminary results jointly obtained by P1&P2. P1 has developed HTS-based tools to study the uridylation status of Arabidopsis transcripts. In a collaborative effort, P1&P2 used such tools to determine the uridylation patterns for six viruses selected from diverse families and including the nepovirus GFLV. Uridylation was detected for all viral RNAs tested, indicating that uridylation is a widespread feature of phytoviruses. Yet, uridylation levels can be extremely diverse between viruses, ranging from less than 1% to more than 90%. Uridylation can be strictly restricted to the addition of a single uridine or corresponds to short U-tails, depending on the viral RNAs. Altogether, those data suggest a complexity and diversity of molecular processes linked to the uridylation of viral RNAs. We will explore this diversity of uridylation-related processes to determine their influence on plant-virus interaction.
URIVir is a basic science project, which aims at understanding fundamental regulatory processes. However, we anticipate that the combined use of model and agronomically relevant viruses will accelerate fundamental discoveries and allow a fast transfer of knowledge to agronomically relevant viruses and crop species. RNA viruses represent 80% of the plant infecting viruses and result in diseases strongly affecting agricultural yields, thereby representing a major threat to food security and economy. Deciphering the molecular bases of RNA virus multiplication and their interactions with the host cellular machinery is therefore crucial to identify novel strategies for developing innovative crop management allowing to reduce damage caused by viral diseases.