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Elife. 2014 Aug 14;3:e03058. doi: 10.7554/eLife.03058.

Considerations when investigating lncRNA function in vivo.

Author information

1
Andrew R Bassett is in the MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom. andrew.bassett@path.ox.ac.uk.
2
Asifa Akhtar is in the Department of Chromatin Regulation, Max-Planck-Institut für Immunbiologie und Epigenetik, Freiburg im Breisgau, Germany.
3
Denise P Barlow is in the CeMM, Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
4
Adrian P Bird is in the Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
5
Neil Brockdorff is in the Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
6
Denis Duboule is in the School of Life Sciences, Ecole Polytechnique Fédérale Lausanne, Lausanne, Switzerland; Department of Genetics and Evolution, Université de Genève, Geneva, Switzerland.
7
Anne Ephrussi is in the Developmental Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
8
Anne C Ferguson-Smith is in the Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
9
Thomas R Gingeras is in the Functional Genomics Group, Cold Spring Harbor Laboratory, Cold Spring Harbor, United States.
10
Wilfried Haerty is in the MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
11
Douglas R Higgs is in the MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom.
12
Eric A Miska is in the Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom; Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
13
Chris P Ponting is in the MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom; Wellcome Trust Sanger Institute, Cambridge, United Kingdom chris.ponting@dpag.ox.ac.uk.

Abstract

Although a small number of the vast array of animal long non-coding RNAs (lncRNAs) have known effects on cellular processes examined in vitro, the extent of their contributions to normal cell processes throughout development, differentiation and disease for the most part remains less clear. Phenotypes arising from deletion of an entire genomic locus cannot be unequivocally attributed either to the loss of the lncRNA per se or to the associated loss of other overlapping DNA regulatory elements. The distinction between cis- or trans-effects is also often problematic. We discuss the advantages and challenges associated with the current techniques for studying the in vivo function of lncRNAs in the light of different models of lncRNA molecular mechanism, and reflect on the design of experiments to mutate lncRNA loci. These considerations should assist in the further investigation of these transcriptional products of the genome.

KEYWORDS:

Science forum; brain development; developmental defect; knockout mouse models; lethality; long non-coding RNAs

PMID:
25124674
PMCID:
PMC4132285
[Indexed for MEDLINE]
Free PMC Article

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