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NON-CODING RNA

Towards a complete map of the human long non-coding RNA transcriptome

Nature Reviews Genetics volume 19, pages 535–548 (2018)Cite this article

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Abstract

Gene maps, or annotations, enable us to navigate the functional landscape of our genome. They are a resource upon which virtually all studies depend, from single-gene to genome-wide scales and from basic molecular biology to medical genetics. Yet present-day annotations suffer from trade-offs between quality and size, with serious but often unappreciated consequences for downstream studies. This is particularly true for long non-coding RNAs (lncRNAs), which are poorly characterized compared to protein-coding genes. Long-read sequencing technologies promise to improve current annotations, paving the way towards a complete annotation of lncRNAs expressed throughout a human lifetime.

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Fig. 1: Basic concepts of lncRNA annotations.
Fig. 2: Annotation strategies for lncRNAs.
Fig. 3: Comparison of leading lncRNA annotations.
Fig. 4: Integrating capture and long-read sequencing with annotation pipelines.

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Acknowledgements

R.J. acknowledges the support of the Swiss National Science Foundation through the National Centres for Competence in Research (NCCR) ‘RNA & Disease’ and the Medical Faculty of the University Hospital and University of Bern. The authors thank J. Carlevaro-Fita (University of Bern) for help with data analysis and J. Harrow (Illumina), J. Mudge (European Bioinformatics Institute), P. Flicek (European Bioinformatics Institute) and I. Jungreis (Massachusetts Institute of Technology) for fruitful discussions and feedback. A.F. is supported by the Wellcome Trust (WT098051 and WT108749/Z/15/Z), the National Human Genome Research Institute (NHGRI) (U41HG007234, 2U41HG007234) and the European Molecular Biology Laboratory. Work described in this publication was supported by the National Human Genome Research Institute of the US National Institutes of Health (grants U41HG007234, U41HG007000 and U54HG007004) and the Wellcome Trust (grant WT098051 to R.G.). Work in the laboratory of R.G. was supported by the National Human Genome Research Institute (awards U54HG007000, R01MH101814 and U41HG007234), the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’ and CERCA Programme/Generalitat de Catalunya. The authors thank the following individuals for administrative support: R. Garrido (Centre for Genomic Regulation) and S. Roesselet and D. Re (both at the University of Bern).

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Nature Reviews Genetics thanks M. Dinger, I. Ulitsky and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Centre of New Technologies, University of Warsaw, Warsaw, Poland

    Barbara Uszczynska-Ratajczak

  2. Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain

    Julien Lagarde & Roderic Guigó

  3. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain

    Julien Lagarde & Roderic Guigó

  4. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK

    Adam Frankish

  5. Department of Medical Oncology, Inselspital, University Hospital and University of Bern, Bern, Switzerland

    Rory Johnson

  6. Department of Biomedical Research (DBMR), University of Bern, Bern, Switzerland

    Rory Johnson

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  1. Barbara Uszczynska-Ratajczak
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  4. Roderic Guigó
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Contributions

B.U.-R. and R.J. researched data for the article. B.U.-R., A.F. and R.J. wrote the article. All authors provided substantial contributions to discussions of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to Rory Johnson.

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RELATED LINKS

buildLoci: https://github.com/julienlag/buildLoci

GENCODE: www.gencodegenes.org

lncrna.annotator: https://github.com/gold-lab/shared_scripts/tree/master/lncRNA.annotator

UniProt: http://www.uniprot.org/

Pfam: http://pfam.xfam.org/

Glossary

Long non-coding RNAs

(lncRNAs). RNA transcripts ≥200 nucleotides long that do not encode any identifiable peptide product.

Annotation

Catalogue of gene loci comprising detailed and hierarchical information on their genomic coordinates and that of their constituent transcript isoforms and exons, all of which are assigned unique and stable identifiers.

Transcriptome assembly

The use of bioinformatic algorithms to reconstruct gene and transcript models based on short sequence reads.

Manual annotation

The creation of gene and transcript models by human annotators based on RNA and protein evidence and according to defined protocols.

Biotype

An annotation label referring to the genomic classification, processing or other characteristics of a locus or transcript intended to provide insights into biological function.

Expressed sequence tags

(ESTs). An early transcriptomic method in which short fragments of transcribed regions, often from 5′ or 3′ ends, are identified through sequencing of cDNA.

Cap analysis of gene expression

(CAGE). A cap-trapping and sequencing method that is considered a gold standard for mapping RNA 5′ ends.

Transcript models

Abstract descriptions of a transcription event, defining the genomic location of the start point, the end point and splice junctions.

Fragments per kilobase per million mapped

(FPKM). One of the principal units of RNA abundance in the context of RNA sequencing experiments, defined as the number of sequenced fragments per kilobase of annotation per million mapped fragments.

Oligonucleotide capture

A method for enriching cDNA libraries with sequences of interest using solution-phase hybridization to tiled, labelled oligonucleotide probes.

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Uszczynska-Ratajczak, B., Lagarde, J., Frankish, A. et al. Towards a complete map of the human long non-coding RNA transcriptome. Nat Rev Genet 19, 535–548 (2018). https://doi.org/10.1038/s41576-018-0017-y

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