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The functions and unique features of long intergenic non-coding RNA

Key Points

  • Long intergenic non-coding RNAs (lincRNAs) are autonomously transcribed RNAs of more than 200 nucleotides in length that do not overlap protein-coding genes. They often lack sequence conservation and have undergone rapid evolution in higher organisms.

  • lincRNAs are distinguished from mRNAs by their lower expression levels and greater tissue specificity, as well as by their biogenesis, degradation and epigenetic regulatory features.

  • The small number of lincRNAs that have been functionally characterized have diverse roles, including enforcing stable and repressive chromatin states that increase or suppress transcriptional activation, orchestrating higher-order nuclear architecture, and acting as protein and RNA scaffolds and decoys.

  • The transcription of lincRNAs can regulate gene neighbourhoods independently of the lincRNA transcripts themselves, suggesting the involvement of enhancer-like activity.

  • lincRNA-derived small open reading frames are rapidly being described and can give rise to functional micropeptides, suggesting the need to revise the definition of some lincRNA loci to coding loci and the potential for loci to possess both coding and non-coding functions.

Abstract

Long intergenic non-coding RNA (lincRNA) genes have diverse features that distinguish them from mRNA-encoding genes and exercise functions such as remodelling chromatin and genome architecture, RNA stabilization and transcription regulation, including enhancer-associated activity. Some genes currently annotated as encoding lincRNAs include small open reading frames (smORFs) and encode functional peptides and thus may be more properly classified as coding RNAs. lincRNAs may broadly serve to fine-tune the expression of neighbouring genes with remarkable tissue specificity through a diversity of mechanisms, highlighting our rapidly evolving understanding of the non-coding genome.

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Figure 1: Distinguishing features of long intergenic non-coding RNAs (lincRNAs) and mRNAs.
Figure 2: Tissue specificity of long intergenic non-coding RNA (lincRNA) expression.
Figure 3: The diverse functions of long intergenic non-coding RNAs (lincRNAs).
Figure 4: Long intergenic non-coding RNAs (lincRNAs) that function through their transcriptional and translational activity.

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Acknowledgements

This work was supported by the US Department of Veterans Affairs (USVA) Office of Research and Development and by the US National Institutes of Health (NIH) AR049737 to P.A.K. and by a Howard Hughes Medical Institute (HHMI) Medical Research Fellowship award to J.D.R. We thank H. Y. Chang and members of the Khavari laboratory for helpful discussions.

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J.D.R., Y.W. and P.A.K. researched data for the article. J.D.R. and P.A.K. made substantial contributions to discussions of the content and wrote and edited the manuscript before submission.

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Correspondence to Paul A. Khavari.

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Ransohoff, J., Wei, Y. & Khavari, P. The functions and unique features of long intergenic non-coding RNA. Nat Rev Mol Cell Biol 19, 143–157 (2018). https://doi.org/10.1038/nrm.2017.104

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