ReviewSmall RNAs derived from longer non-coding RNAs
Highlights
► miRNAs, piRNAs and siRNAs are known as key regulators for accurate cell function. ► Novel classes of small RNAs derived from long non-coding RNAs were discovered recently. ► Small RNAs therefore greatly enlarge the cell’s toolbox for gene regulation.
Introduction
When in 1998 RNA interference (RNAi) was discovered by A. Fire and C. Mello [1], this phenomenon was considered to be a revolutionary tool to study gene function. However, in the last decade endogenous small non-coding RNAs were identified and it became evident that small RNAs form a novel layer of gene regulation with fundamental roles for accurate cell function. MicroRNAs (miRNA) (endogenous) short interfering RNAs (siRNAs, endo-siRNAs) and piwi interacting RNAs (piRNAs) are now known as key regulators of processes as diverse as development, apoptosis, stem cell self-renewal, differentiation and maintenance of cell integrity. Recently, more and more small RNA species deriving from other, longer non-coding RNAs were discovered. Considering the fact that although eukaryotic genomes transcribe up to 90–95% of the genomic DNA, less than 2–3% encode for proteins [2], [3], it is evident that non-coding RNAs might have a more important role than previously thought. Indeed, deep sequencing technologies followed by extensive bioinformatics-based characterization of genomic locations and RNA secondary structure predictions revealed the existence of a vast amount of small RNAs some of them even having miRNA-like functions in posttranscriptional gene regulation. These exciting findings highlight the importance of small RNAs in gene regulation. This review will summarize the most recent findings in the field of small RNAs deriving from longer non-coding RNA species.
Section snippets
Non-coding RNAs (ncRNAs)
Traditionally, ncRNAs are divided into long ncRNAs (>200–300 nucleotides (nt)) and shorter (<200–300 nt) species of ncRNAs (Table 1) [4], [5].
Long ncRNAs, ranging from approximately 200 to several thousands of nt in size, are transcribed by RNA polymerase II, 5′ capped, spliced and polyadenylated [6]. Most examples described to date (reviewed in [6], [7], [8], [9]) are involved in genomic imprinting (such as for example Kcnq1ot1), an epigenetic phenomenon by which a subset of genes is
Small RNAs and the regulation of gene expression
Small RNA-guided posttranscriptional regulation of gene expression is mainly covered by small RNAs (sRNAs) of 18–35 nt in size. In many organisms, the best studied representatives are miRNAs, siRNAs and piRNAs. More recently, ongoing research discovered new classes of sRNA such as endogenous siRNAs (endo-siRNAs), mirtrons, miRNA-like sRNAs derived from longer ncRNAs (tRNAs or snoRNAs), short hairpin RNAs (shRNAs), small vault RNAs (svRNAs), microRNA-offset RNAs (moRs) and QDE2-interacting small
Perspective
Considering the complex relationships between small RNAs, the RNA silencing machinery and their impact on the stable maintenance of the cell, it is evident that identification and characterization of all small RNAs involved in regulatory processes and the discovery of so far unknown modes of regulation by small RNAs is of high biological impact. Many laboratories demonstrate the existence of small RNAs with siRNA-like or miRNA-like functions, however it is important to note that so far only a
Acknowledgements
Our work is supported by a grant from the European research council (ERC, ‘sRNAs’) and the Bayerisches Staatsministerium für Wissenschaft, Forschung und Kunst (BayGene to G.M.). S.R. is supported by an EMBO long term fellowship.
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