Review Article | Published:

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

Nature Reviews Molecular Cell Biology volume 19, pages 143157 (2018) | Download Citation

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.

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.

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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.

Author information

Affiliations

  1. Program in Epithelial Biology, Stanford University School of Medicine, California 94305, USA.

    • Julia D. Ransohoff
    • , Yuning Wei
    •  & Paul A. Khavari
  2. Veterans Affairs Palo Alto Healthcare System, Palo Alto, California 94304, USA.

    • Paul A. Khavari

Authors

  1. Search for Julia D. Ransohoff in:

  2. Search for Yuning Wei in:

  3. Search for Paul A. Khavari in:

Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Paul A. Khavari.

Glossary

Tiling arrays

A method used to probe the transcriptome without prior knowledge of the transcribed loci by hybridizing it to DNA or RNA probes.

Dauer

An alternative developmental stage in nematodes induced by nutrient starvation and characterized by distinct metabolic and morphological features.

Prader–Willi syndrome

A multisystem, genetic disorder secondary to maternal uniparental disomy of the long arm of chromosome 15, or disruption or deletion of the paternal long arm of chromosome 15; characterized by decreased fetal activity, hyperphagia, short stature, mental retardation and hypogonadotropic hypogonadism.

Pseudo-5′-UTR

The region immediately upstream of the first AUG sequence in a long intergenic non-coding RNA.

Tau score

A rank correlation coefficient used to conduct a non-parametric hypothesis test for the statistical correlation between data variables.

Nuclear paraspeckles

Mammalian nuclear organelles, the formation of which is dependent on non-coding RNA species that may have a role in nuclear retention of translatable RNA.

Circular RNAs

Conserved RNAs formed by pre-mRNA back splicing, the function of which may be linked to that of their host genes.

Mediator complex

A conserved protein complex involved in transcription regulation and with multiple roles in gene regulation.

Expression quantitative trait loci

(eQTL). Genetic sequence variants associated with expression changes in one or more local or distant genes; that is, genetic variants that may account for variable gene expression levels.

P-bodies

Cytoplasmic aggregates of messenger ribonucleoproteins associated with mRNA decay machinery and translation inhibition.

About this article

Publication history

Published

DOI

https://doi.org/10.1038/nrm.2017.104