Unexpected selection to retain high GC content and splicing enhancers within exons of multiexonic lncRNA loci

Haerty, Wilfried; Ponting, Chris P.

doi:10.1261/rna.047324.114

Cited by 85 publications

(98 citation statements)

References 95 publications

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“…1 a) as observed by [46]. In addition, multiexonic lincRNAs had overall a higher GC content than monoexonic lincRNAs (Wilcoxon test p -value<10 -6 , Additional file 1: Figure S2) although this pattern was not evident in all species.…”

Section: Resultssupporting

confidence: 55%

Comparative analysis of lincRNA in insect species

2017

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BackgroundThe ever increasing availability of genomes makes it possible to investigate and compare not only the genomic complements of genes and proteins, but also of RNAs. One class of RNAs, the long noncoding RNAs (lncRNAs) and, in particular, their subclass of long intergenic noncoding RNAs (lincRNAs) have recently gained much attention because of their roles in regulation of important biological processes such as immune response or cell differentiation and as possible evolutionary precursors for protein coding genes. lincRNAs seem to be poorly conserved at the sequence level but at least some lincRNAs have conserved structural elements and syntenic genomic positions. Previous studies showed that transposable elements are a main contribution to the evolution of lincRNAs in mammals. In contrast, plant lincRNA emergence and evolution has been linked with local duplication events. However, little is known about their evolutionary dynamics in general and in insect genomes in particular.ResultsHere we compared lincRNAs between seven insect genomes and investigated possible evolutionary changes and functional roles. We find very low sequence conservation between different species and that similarities within a species are mostly due to their association with transposable elements (TE) and simple repeats. Furthermore, we find that TEs are less frequent in lincRNA exons than in their introns, indicating that TEs may have been removed by selection. When we analysed the predicted thermodynamic stabilities of lincRNAs we found that they are more stable than their randomized controls which might indicate some selection pressure to maintain certain structural elements. We list several of the most stable lincRNAs which could serve as prime candidates for future functional studies. We also discuss the possibility of de novo protein coding genes emerging from lincRNAs. This is because lincRNAs with high GC content and potentially with longer open reading frames (ORF) are candidate loci where de novo gene emergence might occur.ConclusionThe processes responsible for the emergence and diversification of lincRNAs in insects remain unclear. Both duplication and transposable elements may be important for the creation of new lincRNAs in insects.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-017-0985-0) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 55%

Comparative analysis of lincRNA in insect species

2017

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“…These splicing-related motifs had a general tendency to appear closer to the 5′ end of the lincRNA (Figure S6A). Two recent studies found that splicing-related motifs are preferentially conserved in lincRNA exons (Schuler et al, 2014; Haerty and Ponting, 2015). Here, we extend these observations to show that such motifs are over-represented in both conserved and lineage-specific lincRNAs.…”

Section: Resultsmentioning

confidence: 99%

Principles of Long Noncoding RNA Evolution Derived from Direct Comparison of Transcriptomes in 17 Species

Hezroni¹,

Koppstein²,

Schwartz³

et al. 2015

Cell Reports

548

642

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Summary The inability to predict long noncoding RNAs from genomic sequence has impeded the use of comparative genomics for studying their biology. Here, we develop methods that use RNA-seq data to annotate the transcriptomes of 16 vertebrates and the echinoid sea urchin, uncovering thousands of previously unannotated genes, most of which produce long intervening noncoding RNAs (lincRNAs). Although in each species >70% of lincRNAs cannot be traced to homologs in species that diverged >50 million years ago, thousands of human lincRNAs have homologs with similar expression patterns in other species. These homologs share short, 5′-biased patches of sequence conservation nested in exonic architectures that have been extensively rewired, in part by transposable element exonization. Thus, over a thousand human lincRNAs are likely to have conserved functions in mammals, and hundreds beyond mammals, but those functions require only short patches of specific sequences and can tolerate major changes in gene architecture.

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“…To address this, we determined if there were differences in exonic splicing enhancers (ESEs), sequence motifs located within exons that regulate alternative splicing (Blencowe 2000). ESEs have been shown to be conserved in lincRNAs (Schüler et al 2014;Haerty and Ponting 2015). We found that ESE density in lincRNAs was higher than in mRNAs, both in human (Fig.…”

Section: Lincrna Splicing Is Inefficientmentioning

confidence: 99%

“…However, recent work has found that a subset of lincRNAs contain conserved regulatory elements, including transcription factor binding sites (Necsulea et al 2014), nuclear localization signals (Hacisuleyman et al 2016), and splicing motifs (Ponjavic et al 2007;Haerty and Ponting 2015). This suggests that the pre-and post-transcriptional regulation of some lincRNAs is functionally relevant.…”

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confidence: 99%

Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs

et al. 2016

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While long intergenic noncoding RNAs (lincRNAs) and mRNAs share similar biogenesis pathways, these transcript classes differ in many regards. LincRNAs are less evolutionarily conserved, less abundant, and more tissue-specific, suggesting that their pre-and post-transcriptional regulation is different from that of mRNAs. Here, we perform an in-depth characterization of the features that contribute to lincRNA regulation in multiple human cell lines. We find that lincRNA promoters are depleted of transcription factor (TF) binding sites, yet enriched for some specific factors such as GATA and FOS relative to mRNA promoters. Surprisingly, we find that H3K9me3-a histone modification typically associated with transcriptional repression-is more enriched at the promoters of active lincRNA loci than at those of active mRNAs. Moreover, H3K9me3-marked lincRNA genes are more tissue-specific. The most discriminant differences between lincRNAs and mRNAs involve splicing. LincRNAs are less efficiently spliced, which cannot be explained by differences in U1 binding or the density of exonic splicing enhancers but may be partially attributed to lower U2AF65 binding and weaker splicing-related motifs. Conversely, the stability of lincRNAs and mRNAs is similar, differing only with regard to the location of stabilizing protein binding sites. Finally, we find that certain transcriptional properties are correlated with higher evolutionary conservation in both DNA and RNA motifs and are enriched in lincRNAs that have been functionally characterized.

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Unexpected selection to retain high GC content and splicing enhancers within exons of multiexonic lncRNA loci

Cited by 85 publications

References 95 publications

Comparative analysis of lincRNA in insect species

Comparative analysis of lincRNA in insect species

Principles of Long Noncoding RNA Evolution Derived from Direct Comparison of Transcriptomes in 17 Species

Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs

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