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International audience; MicroRNAs (miRNAs) are evolutionarily conserved small regulatory RNAs that participate in the adjustment of many, if not all, fundamental biological processes. Molecular mechanisms involved in miRNA biogenesis and mode of action have been elucidated in the past two decades. Similar to many cellular pathways, miRNA processing and function can be globally or specifically regulated at several levels and by numerous proteins and RNAs. Given their role as fine-tuning molecules, it is essential for miRNA expression to be tightly regulated in order to maintain cellular homeostasis. Here, we review our current knowledge of the first step of their maturation occurring in the nucleus and how it can be specifically and dynamically modulated.

Most of the vertebrate genome is transcribed into RNA. Transcribed regions contain hundreds of thousands of potential duplex structures that could serve as substrates for RNAse III enzymes of microRNA (miRNA) maturation pathways. Yet, only a minority of these potential precursors make their way to the cytoplasm to form mature miRNAs. We question here what specific structural features make an RNA stem–loop structure an adequate primary or precursor miRNA. We address this question by comparing known pre-miRNAs to other predicted noncoding transcripts obtained from comparative genomics scans, using the structure comparison program RNAforester. By analyzing a classification tree of 1200 such RNA structures, we observe that pre-miRNAs cluster distinctly from other duplex structures of apparently similar size and free energy. The most distinctive features of nonprecursor duplexes are increased lengths and numbers of bulges and internal loops when compared to real miRNA precursors. Thanks to these characteristics, secondary structure comparison can predict the miRNA precursor status of a candidate stem–loop with a surprising accuracy. Furthermore, predicted noncoding transcripts tend to depart from miRNA precursor characteristics more strongly than randomly occurring duplex structures in genomic DNA. This result suggests that many noncoding RNAs may be under selection to dodge the RNAi pathway.

International audience; RNA interference (RNAi) controls gene expression in eukaryotic cells and thus, cellular homeostasis. In addition, in plants, nematodes and arthropods it is a central antiviral effector mechanism. Antiviral RNAi has been well described as a cell autonomous response, which is triggered by double-stranded RNA (dsRNA) molecules. This dsRNA is the precursor for the silencing of viral RNA in a sequence-specific manner. In plants, systemic antiviral immunity has been demonstrated, however much less is known in animals. Recently, some evidence for a systemic antiviral response in arthropods has come to light. Cell autonomous RNAi may not be sufficient to reach an efficient antiviral response, and the organism might rely on the spread and uptake of an RNAi signal of unknown origin. In this review, we offer a perspective on how RNAi-mediated antiviral immunity could confer systemic protection in insects and we propose directions for future research to understand the mechanism of RNAi-immune signal sorting, spreading and amplification.