Uridylation: a multitasking modification in RNA degradation

Abstract:

Uridylation is a widespread post-transcriptional modification that targets almost all types of RNAs in eukaryotes. Uridylation may promote the maturation or stabilization of certain non-coding RNAs, like the U6 snRNA. However, for most non-coding RNAs, the primordial role of uridylation is to trigger their degradation.

Viral RNAs can also get uridylated across eukaryotic hosts. Yet the molecular consequences of viral RNA uridylation remain mostly unresolved. Our recent survey of plant viral RNA uridylation uncovered an unexpected diversity of 3’ terminal RNA uridylation profiles for representatives of the main families of positive single-stranded RNA phytoviruses(1). I will discuss the potential pro and anti-viral roles of RNA uridylation in plants.

Finally, uridylation also targets mRNAs across eukaryotes, mostly to facilitate their degradation. Using Arabidopsis as a model organism, we have shown that the TUTase URT1 participates in a molecular network connecting several translational repressors/decapping activators(2). This network explains how uridylation at the 3’ end may promote 5’-3’ degradation of mRNAs. In addition, Nanopore direct RNA sequencing reveals a global role of URT1 in shaping poly(A) tail length, notably by preventing the accumulation of excessively deadenylated mRNAs. We propose a model that explains how URT1 could reduce the accumulation of oligo(A)-tailed mRNAs both by favoring their degradation and because 3’ terminal uridines intrinsically hinder deadenylation. Importantly, preventing the accumulation of excessively deadenylated mRNAs avoids the biogenesis of illegitimate siRNAs that silence endogenous mRNAs and perturb Arabidopsis growth and development. We therefore propose that uridylation prevents mRNAs to become a source of toxic non-coding RNAs.

Joly AC, Garcia S, Hily J-M, Koechler S, Demangeat G, Garcia D, Vigne E, Lemaire O, Zuber H, Gagliardi D (2023) An extensive survey of phytoviral RNA 3' uridylation identifies extreme variations and virus-specific patterns. Plant Physiology doi: 10.1093/plphys/kiad278

Lange H and Gagliardi D. (2022) Catalytic activities, molecular connections, and biological functions of plant RNA exosome complexes. The Plant Cell 34: 967–988, doi: org/10.1093/plcell/koab310

Scheer H, de Almeida C, Ferrier E, Simonnot Q, Poirier L, Pflieger D, Sement FM, Koechler S, Piermaria C, Krawczyk P, Mroczek S, Chicher J, Kuhn L, Dziembowski A, Hammann P, Zuber H and Gagliardi D (2021) The TUTase URT1 connects decapping activators and prevents the accumulation of excessively deadenylated mRNAs to avoid siRNA biogenesis. Nature Communications. 12: 1298. doi: 10.1038/s41467-021-21382-2