Review
Non-coding RNAs: key regulators of mammalian transcription

https://doi.org/10.1016/j.tibs.2011.12.003Get rights and content

Non-coding RNAs (ncRNAs) are now recognized as active participants in controlling many biological processes. Indeed, these products of transcription can even control the process of transcription itself. In the past several years, ncRNAs have been found to regulate transcription of single genes, as well as entire transcriptional programs, affecting the expression of hundreds to thousands of genes in response to developmental or environmental signals. Compared to more classical protein regulators, the list of ncRNAs that regulate mRNA transcription in mammalian cells is still small; however, the rate at which new ncRNA transcriptional regulators are being discovered is rapid, suggesting that models for how gene expression is controlled will continue to be redefined as this field develops.

Section snippets

ncRNAs are key regulators of mammalian transcription

The paradigmatic view that the regulation of transcription is mediated solely by protein factors has changed. Indeed, this shift in established thought is occurring throughout biology as ncRNAs are increasingly demonstrated to be active participants in regulating fundamental processes in cells. Moreover, the advent of high-throughput sequencing technologies has revealed that the majority of DNA contained in mammalian genomes is transcribed 1, 2, 3. This finding begs the question of whether all

ncRNAs that control transcription by mediating changes in chromatin structure

The structure of chromatin (the assembly of DNA and histone proteins that constitute eukaryotic genomes) regulates the accessibility of DNA to Pol II and transcription factors, and therefore is integral to transcriptional control. Chromatin structure can be altered by specific post-translational modifications, such as methylation and acetylation, which are added to or removed from the histone proteins. For example, trimethylation of histone H3 lysine 4 (H3K4me3) at promoters of genes and

ncRNAs that directly control the assembly or activity of transcription factor complexes

Multiple ncRNAs have been shown to control gene expression by regulating the activity of transcriptional activators, coregulators, and the general transcription machinery. These ncRNAs are diverse in their mechanisms of action and protein targets. The examples discussed below highlight the ability of ncRNAs to function as scaffolds for the docking of many proteins, to mimic functional DNA elements, and to regulate Pol II itself. It is possible that these examples are representative of what will

Concluding remarks

lncRNAs are becoming widely recognized as key regulators of mammalian transcription, denoting a fundamental shift in paradigm. It appears that lncRNAs evolved to provide an additional layer of control by regulating the protein factors that set transcriptional programs. To date, lncRNAs are known to control many different steps in the process of transcription. This diversity in function points at the potential for lncRNAs to act quite broadly as transcriptional regulators. It is possible that

Acknowledgments

This work was supported by a Public Health Service grant (R01 GM068414) from the National Institute of General Medical Sciences.

Glossary

ChIP-chip
a technique to determine the sites across the genome that are occupied by a protein. An antibody is used to purify a protein and any associated chromatin from formaldehyde crosslinked cells (ChIP, chromatin immunoprecipitation). After reversing the crosslinks, the chromatin is hybridized to a microarray (chip) containing genomic sequences to determine the regions to which the protein is bound in cells. The chromatin can also be deep-sequenced (ChIP-seq) to determine the genome-wide

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