Biogenesis of small RNAs in animals

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Abstract
Recent progress in high-throughput sequencing has uncovered an astounding landscape of small RNAs in eukaryotic cells. Various small RNAs of distinctive characteristics have been found and can be classified into three classes based on their biogenesis mechanism and the type of Argonaute (Ago) protein that they are associated with. MicroRNAs (miRNAs) are generated from local hairpin structures by the action of two RNase III-type proteins, Drosha and Dicer. Mature ∼22-nucleotide (nt) miRNAs are then bound by Ago-subfamily proteins. miRNAs target mRNAs and thereby function as post-transcriptional regulators. Piwi-interacting RNAs (piRNAs), which are 24–31 nt in length, are associated with Piwi-subfamily proteins. The biogenesis of piRNAs does not depend on Dicer. At least some piRNAs are involved in transposon silencing through heterochromatin formation or RNA destabilization. Endogenous small interfering RNAs (endo-siRNAs), such as miRNAs, associate with Ago-subfamily proteins. However, endo-siRNAs differ from miRNAs in that they are derived from long double-stranded RNAs and are dependent only on Dicer but not on Drosha. They are also slightly shorter (∼21 nt) than miRNAs. At least some of the endo-siRNAs have been shown to function as post-transcriptional regulators that target RNAs. There are numerous other small RNAs that are generated through non-canonical pathways. Many of them are difficult to classify and their biogenesis pathways remain poorly understood, but they may have species-specific functions that are not yet fully appreciated.