Small rna sorting matchmaking for argonautes

Functional small RNAs are generated from select miRNA hairpin loops in flies and mammals

A general feature of Argonaute-dependent small RNAs is their base-paired precursor structures, and precursor duplex structures are often required for confident annotation of miRNA genes. However, this rule has been broken by discoveries of functional small RNA species whose precursors lack a predictable double-stranded ds- RNA structure, arguing that duplex structures are not prerequisite for small RNA loading to Argonautes. The biological significance of single-stranded ss- RNA loading has been recognized particularly in systems where active small RNA amplification mechanisms are involved, because even a small amount of RNA molecules can trigger the production of abundant RNA species leading to profound biological effects. However, even in the absence of small RNA amplification mechanisms, recent studies have demonstrated that potent gene silencing can be achieved using chemically modified synthetic ssRNAs that are resistant to RNases in mice. Therefore, such ssRNA-mediated gene regulation may have broader roles than previously recognized, and the findings have opened the door for further research to optimize the design of ss-siRNAs toward future pharmaceutical and biomedical applications of gene silencing technologies. Therefore, it appeared that double-stranded structures were prerequisite to the initiation of this mysterious silencing mechanism.

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The terminal loops of some miRNA hairpins regulate processing efficiency, but once liberated by Dicer, they are generally considered nonfunctional by-products. This was unexpected, since endogenous loading of Argonaute proteins was believed to occur exclusively via small RNA duplexes. Using in vitro assays, which recapitulate Argonaute-specific loop loading from synthetic pre-miRNAs and even single-stranded oligoribonucleotides corresponding to miRNA loops, we reveal that the loop-loading mechanism is distinct from duplex loading.

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However, the roles of phasiRNAs remain largely unknown. The development of imaging technology and RNA profiling has clarified the spatiotemporal regulation of phasiRNAs, and subsequently the different functions of nt trans -acting phasiRNAs and nt cis -regulatory phasiRNAs during male organ development.

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Small RNA sorting: matchmaking for Argonautes

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