Journal Article

Small RNA sorting: matchmaking for Argonautes

Hannon, Gregory J., Czech, Benjamin

2011

Overview

Key Points Small RNAs are defined by their size (~20–30 nucleotides in length) and their association with members of the Argonaute family. They impact nearly every biological process in eukaryotic cells, directly or indirectly. MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) are born from dsRNA precursors, whereas Piwi-interacting RNAs (piRNAs) originate from single-stranded transcripts. To perform their myriad roles, different classes of small RNAs must not only be generated in a precise manner, but must also be sorted into specific Argonaute complexes. An Argonaute protein primed with a single-stranded small RNA is called an RNA-induced silencing complex (RISC). Eukaryotic organisms often encode several Argonaute proteins that function in distinct pathways. They typically show various preferences for the small RNAs they accept, comprising loading determinants that include the identity of terminal nucleotides, small RNA duplex structure and thermodynamic properties. Small RNA duplexes are usually not incorporated into Argonaute proteins without assistance from additional protein factors, known as the RISC-loading machinery. miRNAs and siRNAs arise from small RNA duplexes and are loaded into Argonaute as dsRNA molecules. Thus, during RISC maturation, one strand must be selected specifically, whereas the other strand must be lost or degraded. Mature RISC regulates targets through sequence complementarity. The ultimate impact of accurate strand selection and sorting is that an active RISC is formed, imbued with the ability to regulate target transcripts. Biogenesis and sorting of small RNAs in animals and plants share some key mechanistic features, but have also evolved myriad variations and adaptations. To achieve their diverse regulatory functions, specific small RNA strands need to pair with the correct Argonaute protein partners. This Review discusses the recent substantial progress in understanding how small RNA sorting occurs in animals and plants. Small RNAs directly or indirectly impact nearly every biological process in eukaryotic cells. To perform their myriad roles, not only must precise small RNA species be generated, but they must also be loaded into specific effector complexes called RNA-induced silencing complexes (RISCs). Argonaute proteins form the core of RISCs and different members of this large family have specific expression patterns, protein binding partners and biochemical capabilities. In this Review, we explore the mechanisms that pair specific small RNA strands with their partner proteins, with an eye towards the substantial progress that has been recently made in understanding the sorting of the major small RNA classes — microRNAs (miRNAs) and small interfering RNAs (siRNAs) — in plants and animals.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/337/1645 / 631/337/384/521 / Agriculture / Animal Genetics and Genomics / Animals / Biomedical and Life Sciences / Biomedicine / Biosynthesis / Cancer Research / Diptera - metabolism / Enzymes / Eukaryotic Initiation Factors - metabolism / Gene expression / Gene Function / Human Genetics / Humans / MicroRNAs / MicroRNAs - metabolism / Physiological aspects / Plants - metabolism / Protein binding / Proteins / review-article / RNA / RNA polymerase / RNA Transport / RNA, Double-Stranded - metabolism / RNA, Small Interfering - metabolism / RNA-Induced Silencing Complex - metabolism