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Figure 2. Structure and mechanisms of action of eukaryotic miRNA and prokaryotic sRNA. Left panel: miRNA genes are transcribed into pri-miRNA and undergo processes to liberate pre-miRNA that are exported to the cytoplasm. Pre-miRNAs are then further cleaved by the enzyme Dicer. The miRNA duplex is then loaded into an AGO, to form the RISC after expulsion of the passenger strand. A: A perfect base pairing between a miRNA and its target 3’ UTR sequence triggers an endonucleolytic mRNA cleavage induced by AGO. B: The formation of a partial duplex (imperfect base pairing) in the 3’ UTR destabilizes mRNA through the recruitment of TNRC6 proteins and the CCR4-NOT complexes, which induce mRNA deadenylation. CCR4-NOT further inhibits translation, notably through the recruitment of a helicase. C: An extensive 3’-end pairing on the CDS, without a strong seed pairing, induces ribosome stalling and, therefore, inhibits mRNA translation. D: Under specific conditions, such as amino-acid starvation or cell cycle arrest, miRNA binding to the 3’ or 5’ UTR can upregulate translation in an unknown process involving the miRNA binding proteins AGO2 and FXR1. Right panel: Prokaryotic sRNAs originate from intergenic regions, 5’ or 3’ UTRs, or are derived from existing RNA elements. The sRNA regulatory mechanisms described are limited to Hfq-mediated pairing, although other chaperone proteins and Hfq-independent mechanisms exist. A: sRNA pairing to the RBS, including the SD sequence or the AUG start codon, limits ribosome assembly and hinders translation initiation. B: sRNA pairing in the 5’ UTR or CDS recruits RNase E and induces mRNA degradation. C: On the 5’ UTR or CDS, sRNA can stabilize mRNA secondary structure or bind to RNase cleavage sites and protect RNase-sensitive mRNA from degradation, thereby upregulating translation. D: sRNA binding at the 5’ UTR can help unfolding mRNA to reveal sequestered RBS and facilitate ribosome binding and translation. Created with BioRender.com. miRNA: MicroRNA; sRNA: small RNA; pri-miRNA: primary miRNA; pre-miRNA: precursor miRNA; AGO: Argonaute protein; RISC: RNA-induced silencing complex; UTR: untranslated region; CDS: coding sequence; RBS: ribosome binding site; SD: Shine-Dalgarno; RNase: ribonuclease.