Abstract

Non-coding RNAs are dominant in the genomic output of the higher organisms being not simply occasional transcripts with idiosyncratic functions, but constituting an extensive regulatory network. Among all the species of non-coding RNAs, small non-coding RNAs (miRNAs, siRNAs and piRNAs) have been shown to be in the core of the regulatory machinery of all the genomic output in eukaryotic cells. Small non-coding RNAs are produced by several pathways containing specialized enzymes that process RNA transcripts. The mechanism of action of these molecules is also ensured by a group of effector proteins that are commonly engaged within high molecular weight protein-RNA complexes. In the last decade, the contribution of structural biology has been essential to the dissection of the molecular mechanisms involved in the biosynthesis and function of small non-coding RNAs.

Highlights

  • The central dogma of biology holds that genetic information normally flows from DNA to RNA and to proteins

  • The first step in the biosynthesis of miRNAs in animal and insect cells is catalyzed by a tandem of proteins that form the microprocessor complex: Drosha, a type III RNAse and DGCR8, a dsRNA-binding protein responsible for the recognition of specific hairpin loops [20,71]

  • AGO proteins are present in different extend from budding yeasts to mammals. They constitute the core of the RNA induced silencing complexes in the cytoplasm (RISC complex) and in the nucleus (RITS complex) [97,98]

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Summary

Introduction

The central dogma of biology holds that genetic information normally flows from DNA to RNA and to proteins. Some ncRNAs are derived from the further processing of exons such the miRNAs produced by some transcripts, and of introns of both protein coding and ncRNA genes as exemplified by snoRNAs. There are three major families of small non-coding RNAs (ncRNAs) in eukaryotic cells: micro-RNAs (miRNAs), piRNAs and small-interfering RNAs (siRNAs). There are three major families of small non-coding RNAs (ncRNAs) in eukaryotic cells: micro-RNAs (miRNAs), piRNAs and small-interfering RNAs (siRNAs) These families are different in their origin, but they share specific steps in their biosynthetic pathways and regulatory mechanisms (Figure 1). In this review we will summarize these contributions, with special emphasis to the human key proteins involved in the biosynthesis and function of small ncRNAs. RNAs (siRNAs) are generated by nucleases (Drosha and Dicer) from dsRNA precursors, whereas PIWI-interacting RNAs (piRNAs) are produced from long single-stranded RNA precursors by an already not completely understood mechanism. The key challenge will be to understand the real role of endogenous siRNA, those that will target protein coding genes and how they regulate mRNA expression

Small Non-Coding RNA Processors
Drosha and the Nuclear Microprocessor
Cytoplasmic Processors
Efectors of the Small Non-Coding RNA Regulatory Networks
AGO Sub-Family
Other Members of the AGO Sub-Family
PIWI Proteins
Other Helper Proteins
Conclusions
Findings
Methods
Full Text
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