Evolution to the rescue: using comparative genomics to understand long non-coding RNAs

Long non-coding RNAs (lncRNAs) have emerged in recent years as major players in a multitude of pathways across species, but it remains challenging to understand which of them are important and how their functions are performed. Comparative sequence analysis has been instrumental for studying proteins and small RNAs, but the rapid evolution of lncRNAs poses new challenges that demand new approaches. Here, I review the lessons learned so far from genome-wide mapping and comparisons of lncRNAs across different species. I also discuss how comparative analyses can help us to understand lncRNA function and provide practical considerations for examining functional conservation of lncRNA genes.

[1]  Steven L Salzberg,et al.  HISAT: a fast spliced aligner with low memory requirements , 2015, Nature Methods.

[2]  Steven R. Eichten,et al.  Genome-wide discovery and characterization of maize long non-coding RNAs , 2014, Genome Biology.

[3]  D. Bartel,et al.  Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species. , 2015, Cell reports.

[4]  R. Hardison,et al.  Unlinking an lncRNA from Its Associated cis Element. , 2016, Molecular cell.

[5]  S. Freier,et al.  Regulation of the ESC transcriptome by nuclear long noncoding RNAs , 2015, Genome research.

[6]  J. Mattick,et al.  Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome. , 2005, Genome research.

[7]  Carlos Eduardo Ferreira,et al.  Advances in Bioinformatics and Computational Biology, 5th Brazilian Symposium on Bioinformatics, BSB 2010, Rio de Janeiro, Brazil, August 31-September 3, 2010. Proceedings , 2010, BSB.

[8]  Frank Grützner,et al.  The evolution of lncRNA repertoires and expression patterns in tetrapods , 2014, Nature.

[9]  S. Dhanasekaran,et al.  The landscape of long noncoding RNAs in the human transcriptome , 2015, Nature Genetics.

[10]  J. Rinn,et al.  linc-HOXA1 is a noncoding RNA that represses Hoxa1 transcription in cis. , 2013, Genes & development.

[11]  David R. Kelley,et al.  Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks , 2012, Nature Protocols.

[12]  N. Chua,et al.  Genome-Wide Analysis Uncovers Regulation of Long Intergenic Noncoding RNAs in Arabidopsis[C][W] , 2012, Plant Cell.

[13]  N. Friedman,et al.  Trinity: reconstructing a full-length transcriptome without a genome from RNA-Seq data , 2011, Nature Biotechnology.

[14]  Zev N. Kronenberg,et al.  Transposable Elements Are Major Contributors to the Origin, Diversification, and Regulation of Vertebrate Long Noncoding RNAs , 2013, PLoS genetics.

[15]  N. Brockdorff,et al.  A Dual Origin of the Xist Gene from a Protein-Coding Gene and a Set of Transposable Elements , 2008, PloS one.

[16]  J. Nielsen,et al.  Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics* , 2013, Molecular & Cellular Proteomics.

[17]  Aviv Regev,et al.  Comprehensive comparative analysis of RNA sequencing methods for degraded or low input samples , 2013, Nature Methods.

[18]  Z. Yang,et al.  Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. , 1998, Molecular biology and evolution.

[19]  D. Bartel MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[20]  Andreu Paytuví Gallart,et al.  GREENC: a Wiki-based database of plant lncRNAs , 2015, Nucleic Acids Res..

[21]  Maojun Wang,et al.  Long noncoding RNAs and their proposed functions in fibre development of cotton (Gossypium spp.). , 2015, The New phytologist.

[22]  J. Harrow,et al.  Systematic evaluation of spliced alignment programs for RNA-seq data , 2013, Nature Methods.

[23]  K. Pollard,et al.  Detection of nonneutral substitution rates on mammalian phylogenies. , 2010, Genome research.

[24]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[25]  S. Salzberg,et al.  StringTie enables improved reconstruction of a transcriptome from RNA-seq reads , 2015, Nature Biotechnology.

[26]  J. Steitz,et al.  Conservation of a triple-helix-forming RNA stability element in noncoding and genomic RNAs of diverse viruses. , 2012, Cell reports.

[27]  Wilfried Haerty,et al.  Considerations when investigating lncRNA function in vivo , 2014, eLife.

[28]  Daniel J. Blankenberg,et al.  28-way vertebrate alignment and conservation track in the UCSC Genome Browser. , 2007, Genome research.

[29]  Robert M. Waterhouse,et al.  Long non-coding RNA discovery across the genus anopheles reveals conserved secondary structures within and beyond the Gambiae complex , 2015, BMC Genomics.

[30]  David R. Kelley,et al.  Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre , 2014, Nature Structural &Molecular Biology.

[31]  Vincent L. Butty,et al.  Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment , 2013, Cell.

[32]  Stephen J. Tapscott,et al.  DUX4 Binding to Retroelements Creates Promoters That Are Active in FSHD Muscle and Testis , 2013, PLoS genetics.

[33]  I. Clay,et al.  A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation. , 2015, Developmental cell.

[34]  Henrik Kaessmann,et al.  Origins, evolution, and phenotypic impact of new genes. , 2010, Genome research.

[35]  Phillip A Sharp,et al.  A triple helix stabilizes the 3' ends of long noncoding RNAs that lack poly(A) tails. , 2012, Genes & development.

[36]  Ram Samudrala,et al.  Mouse transcriptome: Neutral evolution of ‘non-coding’ complementary DNAs , 2004, Nature.

[37]  C. Ponting,et al.  Unexpected selection to retain high GC content and splicing enhancers within exons of multiexonic lncRNA loci , 2015, RNA.

[38]  T. Mikkelsen,et al.  Cellular source and mechanisms of high transcriptome complexity in the mammalian testis. , 2013, Cell reports.

[39]  Jianzhi Zhang,et al.  Human long noncoding RNAs are substantially less folded than messenger RNAs. , 2015, Molecular biology and evolution.

[40]  Cole Trapnell,et al.  Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. , 2011, Genes & development.

[41]  S. Itzkovitz,et al.  A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells , 2015, Nature Communications.

[42]  Sarah W. Burge,et al.  Conservation and Losses of Non-Coding RNAs in Avian Genomes , 2015, PloS one.

[43]  J. Pires,et al.  Positionally-conserved but sequence-diverged: identification of long non-coding RNAs in the Brassicaceae and Cleomaceae , 2015, BMC Plant Biology.

[44]  Selene L. Fernandez-Valverde,et al.  Dynamic and Widespread lncRNA Expression in a Sponge and the Origin of Animal Complexity , 2015, Molecular biology and evolution.

[45]  B. Reinhart,et al.  Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA , 2000, Nature.

[46]  Howard Y. Chang,et al.  Targeted disruption of Hotair leads to homeotic transformation and gene derepression. , 2013, Cell reports.

[47]  Rolf Backofen,et al.  Tandem stem-loops in roX RNAs act together to mediate X chromosome dosage compensation in Drosophila. , 2013, Molecular cell.

[48]  A. Regev,et al.  Evolutionary analysis across mammals reveals distinct classes of long non-coding RNAs , 2015, Genome Biology.

[49]  Sebastian D. Mackowiak,et al.  Circular RNAs are a large class of animal RNAs with regulatory potency , 2013, Nature.

[50]  F. Pauler,et al.  Airn Transcriptional Overlap, But Not Its lncRNA Products, Induces Imprinted Igf2r Silencing , 2012, Science.

[51]  Anna Marie Pyle,et al.  HOTAIR forms an intricate and modular secondary structure. , 2015, Molecular cell.

[52]  P. Avner,et al.  Human XIST yeast artificial chromosome transgenes show partial X inactivation center function in mouse embryonic stem cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[53]  Laurence Ettwiller,et al.  Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor , 2011, Nature Genetics.

[54]  Lior Pachter,et al.  Sequence Analysis , 2020, Definitions.

[55]  D. Bartel,et al.  Long noncoding RNAs in C. elegans , 2012, Genome research.

[56]  K. Zhao,et al.  Corrigendum: The conservation and signatures of lincRNAs in Marek’s disease of chicken , 2016, Scientific Reports.

[57]  David R. Kelley,et al.  Transposable elements reveal a stem cell-specific class of long noncoding RNAs , 2012, Genome Biology.

[58]  Patrick Schorderet,et al.  Structural and Functional Differences in the Long Non-Coding RNA Hotair in Mouse and Human , 2011, PLoS genetics.

[59]  Jill P. Mesirov,et al.  RNA Duplex Map in Living Cells Reveals Higher-Order Transcriptome Structure , 2016, Cell.

[60]  Svetlana A. Shabalina,et al.  Negative Correlation between Expression Level and Evolutionary Rate of Long Intergenic Noncoding RNAs , 2011, Genome biology and evolution.

[61]  Spitale Robert,et al.  Structural imprints in vivo decode RNA regulatory mechanisms , 2016 .

[62]  Wilfried Haerty,et al.  Mutations within lncRNAs are effectively selected against in fruitfly but not in human , 2013, Genome Biology.

[63]  K. Palczewski,et al.  Evolutionarily conserved long intergenic non-coding RNAs in the eye. , 2013, Human molecular genetics.

[64]  J. Harrow,et al.  Assessment of transcript reconstruction methods for RNA-seq , 2013, Nature Methods.

[65]  Manolis Kellis,et al.  Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals , 2014, Genome research.

[66]  Gérard Pierron,et al.  Functional conservation of the lncRNA NEAT1 in the ancestrally diverged marsupial lineage: Evidence for NEAT1 expression and associated paraspeckle assembly during late gestation in the opossum Monodelphis domestica , 2016, RNA biology.

[67]  C. Rougeulle,et al.  Origin and evolution of the long non-coding genes in the X-inactivation center. , 2011, Biochimie.

[68]  L. Lipovich,et al.  Activity-Dependent Human Brain Coding/Noncoding Gene Regulatory Networks , 2012, Genetics.

[69]  C. Betsholtz,et al.  Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish. , 2015, Developmental cell.

[70]  J. Bixby,et al.  Isoform Diversity and Regulation in Peripheral and Central Neurons Revealed through RNA-Seq , 2012, PloS one.

[71]  Piero Carninci,et al.  Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat , 2012, Nature.

[72]  Laurent Duret,et al.  The Xist RNA Gene Evolved in Eutherians by Pseudogenization of a Protein-Coding Gene , 2006, Science.

[73]  Howard Y. Chang,et al.  Rapid evolutionary turnover underlies conserved lncRNA–genome interactions , 2016, Genes & development.

[74]  M. Monk,et al.  Regulation of X-Chromosome Inactivation in Development in Mice and Humans , 1998, Microbiology and Molecular Biology Reviews.

[75]  W. Terzaghi,et al.  Arabidopsis noncoding RNA mediates control of photomorphogenesis by red light , 2014, Proceedings of the National Academy of Sciences.

[76]  C. Ponting,et al.  Long noncoding RNA genes: conservation of sequence and brain expression among diverse amniotes , 2010, Genome Biology.

[77]  Jun Liu,et al.  Analysis of non-coding transcriptome in rice and maize uncovers roles of conserved lncRNAs associated with agriculture traits. , 2015, The Plant journal : for cell and molecular biology.

[78]  M. Dinger,et al.  Endogenous microRNA sponges: evidence and controversy , 2016, Nature Reviews Genetics.

[79]  Rui Liu,et al.  The lncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression. , 2015, Cell reports.

[80]  Nicholas W. VanKuren,et al.  New gene evolution: little did we know. , 2013, Annual review of genetics.

[81]  Caleb Webber,et al.  Extensive microRNA-mediated crosstalk between lncRNAs and mRNAs in mouse embryonic stem cells , 2015, Genome research.

[82]  James B. Brown,et al.  Diversity and dynamics of the Drosophila transcriptome , 2014, Nature.

[83]  Igor Ulitsky,et al.  Methods for distinguishing between protein-coding and long noncoding RNAs and the elusive biological purpose of translation of long noncoding RNAs , 2015, bioRxiv.

[84]  Phillip A. Sharp,et al.  Divergent Transcription: A Driving Force for New Gene Origination? , 2013, Cell.

[85]  C. Shin,et al.  Genome-wide characterization of long intergenic non-coding RNAs (lincRNAs) provides new insight into viral diseases in honey bees Apis cerana and Apis mellifera , 2015, BMC Genomics.

[86]  Tsung-Cheng Chang,et al.  Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins , 2016, Cell.

[87]  R. Guigó,et al.  The RIDL hypothesis: transposable elements as functional domains of long noncoding RNAs , 2014, RNA.

[88]  G. Elgar,et al.  Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation , 2012, Nature.

[89]  P. Avner,et al.  2-D Structure of the A Region of Xist RNA and Its Implication for PRC2 Association , 2010, PLoS biology.

[90]  Peter F. Stadler,et al.  Alu Elements in ANRIL Non-Coding RNA at Chromosome 9p21 Modulate Atherogenic Cell Functions through Trans-Regulation of Gene Networks , 2013, PLoS genetics.

[91]  W. L. Ruzzo,et al.  De novo prediction of structured RNAs from genomic sequences. , 2010, Trends in biotechnology.

[92]  Denise P Barlow,et al.  Gene regulation by the act of long non-coding RNA transcription , 2013, BMC Biology.

[93]  Gene W. Yeo,et al.  Identification of Novel Long Noncoding RNAs Underlying Vertebrate Cardiovascular Development , 2015, Circulation.

[94]  M. Batzer,et al.  The impact of retrotransposons on human genome evolution , 2009, Nature Reviews Genetics.

[95]  D. Bartel,et al.  lincRNAs: Genomics, Evolution, and Mechanisms , 2013, Cell.

[96]  T. Jensen,et al.  Dealing with pervasive transcription. , 2013, Molecular cell.

[97]  Wing H Wong,et al.  The primate-specific noncoding RNA HPAT5 regulates pluripotency during human preimplantation development and nuclear reprogramming , 2015, Nature Genetics.

[98]  R. Guigó,et al.  CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis. , 2015, Journal of molecular and cellular cardiology.

[99]  B. Migeon,et al.  Human X inactivation center induces random X chromosome inactivation in male transgenic mice. , 1999, Genomics.

[100]  C. Ponting,et al.  Catalogues of mammalian long noncoding RNAs: modest conservation and incompleteness , 2009, Genome Biology.

[101]  Eugene Berezikov,et al.  Evolution of microRNA diversity and regulation in animals , 2011, Nature Reviews Genetics.

[102]  M. Takeichi,et al.  The mRNA-like noncoding RNA Gomafu constitutes a novel nuclear domain in a subset of neurons , 2007, Journal of Cell Science.

[103]  J. Gorodkin,et al.  Thousands of corresponding human and mouse genomic regions unalignable in primary sequence contain common RNA structure. , 2006, Genome research.

[104]  Sean R. Eddy,et al.  Infernal 1.1: 100-fold faster RNA homology searches , 2013, Bioinform..

[105]  Valer Gotea,et al.  Bidirectional Promoters as Important Drivers for the Emergence of Species-Specific Transcripts , 2013, PloS one.

[106]  Gene W. Yeo,et al.  Divergent Transcription from Active Promoters , 2008, Science.

[107]  Chris P. Ponting,et al.  Rapid Turnover of Long Noncoding RNAs and the Evolution of Gene Expression , 2012, PLoS genetics.

[108]  Yi Zhao,et al.  Evolutionary annotation of conserved long non-coding RNAs in major mammalian species , 2015, Science China Life Sciences.

[109]  T. Derrien,et al.  Identification of long non-coding RNAs in insects genomes. , 2015, Current opinion in insect science.

[110]  Jon Bråte,et al.  Regulatory RNA at the root of animals: dynamic expression of developmental lincRNAs in the calcisponge Sycon ciliatum , 2015, Proceedings of the Royal Society B: Biological Sciences.

[111]  Michael F. Lin,et al.  Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals , 2009, Nature.

[112]  David P. Bartel,et al.  Beyond Secondary Structure: Primary-Sequence Determinants License Pri-miRNA Hairpins for Processing , 2013, Cell.

[113]  P. Stadler,et al.  Widespread purifying selection on RNA structure in mammals , 2013, Nucleic acids research.

[114]  C. David Page,et al.  Human pluripotent stem cell-derived neural constructs for predicting neural toxicity , 2015, Proceedings of the National Academy of Sciences.

[115]  Mihaela Zavolan,et al.  Comparative assessment of methods for the computational inference of transcript isoform abundance from RNA-seq data , 2015, Genome Biology.

[116]  Howard Y. Chang,et al.  Long noncoding RNAs and human disease. , 2011, Trends in cell biology.

[117]  L. Qu,et al.  Genome-wide screening and functional analysis identify a large number of long noncoding RNAs involved in the sexual reproduction of rice , 2014, Genome Biology.

[118]  Chinmay J. Shukla,et al.  Function and evolution of local repeats in the Firre locus , 2016, Nature Communications.

[119]  Monika S. Kowalczyk,et al.  Chromatin signatures at transcriptional start sites separate two equally populated yet distinct classes of intergenic long noncoding RNAs , 2013, Genome Biology.

[120]  C. Perou,et al.  Comparison of RNA-Seq by poly (A) capture, ribosomal RNA depletion, and DNA microarray for expression profiling , 2014, BMC Genomics.

[121]  C. Ponting,et al.  Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs. , 2007, Genome research.

[122]  J. Rinn,et al.  Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution , 2015, Genome Biology.

[123]  Howard Y. Chang,et al.  Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs , 2007, Cell.

[124]  M. McCarthy,et al.  Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. , 2012, Cell metabolism.

[125]  An-Yuan Guo,et al.  lncRNASNP: a database of SNPs in lncRNAs and their potential functions in human and mouse , 2014, Nucleic Acids Res..

[126]  S. Orkin,et al.  Opposing Roles for the lncRNA Haunt and Its Genomic Locus in Regulating HOXA Gene Activation during Embryonic Stem Cell Differentiation. , 2015, Cell stem cell.

[127]  Peter F. Stadler,et al.  Evolution of the Long Non-coding RNAs MALAT1 and MENbeta/epsilon , 2010, BSB.

[128]  Cole Trapnell,et al.  Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. , 2010, Nature biotechnology.

[129]  Jeannie T. Lee,et al.  Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome , 2008, Science.

[130]  M. Kuroda,et al.  Regulation of Histone H4 Lys16 Acetylation by Predicted Alternative Secondary Structures in roX Noncoding RNAs , 2008, Molecular and Cellular Biology.

[131]  D. Bartel,et al.  Conserved Function of lincRNAs in Vertebrate Embryonic Development despite Rapid Sequence Evolution , 2011, Cell.

[132]  T. Mituyama,et al.  MENε/β noncoding RNAs are essential for structural integrity of nuclear paraspeckles , 2009, Proceedings of the National Academy of Sciences.