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Long non-coding RNAs: insights into functions

Abstract

In mammals and other eukaryotes most of the genome is transcribed in a developmentally regulated manner to produce large numbers of long non-coding RNAs (ncRNAs). Here we review the rapidly advancing field of long ncRNAs, describing their conservation, their organization in the genome and their roles in gene regulation. We also consider the medical implications, and the emerging recognition that any transcript, regardless of coding potential, can have an intrinsic function as an RNA.

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Figure 1: Genomic organization of coding and non-coding transcripts.
Figure 2: Functions of long non-coding RNAs (ncRNAs).

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Acknowledgements

We thank P. Amaral and other laboratory colleagues for many discussions related to this article, and the Australian Research Council for financial support. We apologize both to readers and colleagues for references that were omitted owing to editorial constraint.

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Correspondence to John S. Mattick.

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FURTHER INFORMATION

Mattick laboratory web site

CPC (coding potential calculator)

NRED (ncRNA expression database)

RNAdb (RNA database)

Glossary

Adaptive radiation

Evolution of new morphological or functional characteristics in lineages that diversify in response to environmental changes or to enable colonization of new ecological niches.

Epigenetic

Heritable changes in phenotype caused by mechanisms outside of the genomic sequence. Such changes might remain through cell divisions during, for example, cellular differentiation, or they might persist through subsequent generations. Epigenetic changes include chromatin modifications, such as histone acetylation, or chemical alterations to the DNA itself, such as DNA methylation.

Long ncRNA

Transcripts longer than 200 nucleotides that have little or no protein-coding capacity. Long ncRNAs can regulate gene expression through a diversity of mechanisms.

MicroRNA

Single-stranded RNAs of approximately 21–23 nucleotides that regulate gene expression by partial complementary base pairing to specific mRNAs. This annealing inhibits protein translation and can also facilitate degradation of the target mRNA.

Transvection

Apparent cross-talk between alleles on homologous chromosomes, in which complementation is observed between promoter mutations in one allele and structural mutations in the other. Transvection can cause either gene activation or repression.

X chromosome inactivation

A process in which one of the two copies of the X chromosomes in female mammals is inactivated. X inactivation occurs so that females produce the same dosage of gene products from the X chromosome as males.

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Mercer, T., Dinger, M. & Mattick, J. Long non-coding RNAs: insights into functions. Nat Rev Genet 10, 155–159 (2009). https://doi.org/10.1038/nrg2521

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