Genomic and Transcriptional Co-Localization of Protein-Coding and Long Non-Coding RNA Pairs in the Developing Brain

Ponjavic, Jasmina; Oliver, Peter L.; Lunter, Gerton; Ponting, Chris P.

doi:10.1371/journal.pgen.1000617

Cited by 343 publications

(365 citation statements)

References 58 publications

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“…Finally, protein-coding genes proximal (#10 kb) to lincRNAs are enriched for those associated with development and transcriptional regulation (e.g., GATA2, GZF1, and NEUROG2 all have lincRNA neighbors) (Supplemental Fig. 3), consistent with previous reports (Guttman et al 2009;Ponjavic et al 2009). …”

Section: A Stringent Set Of 4662 Human Lincrnassupporting

confidence: 89%

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Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses

Cabili¹,

Trapnell²,

Goff³

et al. 2011

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Large intergenic noncoding RNAs (lincRNAs) are emerging as key regulators of diverse cellular processes. Determining the function of individual lincRNAs remains a challenge. Recent advances in RNA sequencing (RNA-seq) and computational methods allow for an unprecedented analysis of such transcripts. Here, we present an integrative approach to define a reference catalog of >8000 human lincRNAs. Our catalog unifies previously existing annotation sources with transcripts we assembled from RNA-seq data collected from~4 billion RNA-seq reads across 24 tissues and cell types. We characterize each lincRNA by a panorama of >30 properties, including sequence, structural, transcriptional, and orthology features. We found that lincRNA expression is strikingly tissue-specific compared with coding genes, and that lincRNAs are typically coexpressed with their neighboring genes, albeit to an extent similar to that of pairs of neighboring protein-coding genes. We distinguish an additional subset of transcripts that have high evolutionary conservation but may include short ORFs and may serve as either lincRNAs or small peptides. Our integrated, comprehensive, yet conservative reference catalog of human lincRNAs reveals the global properties of lincRNAs and will facilitate experimental studies and further functional classification of these genes.

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Section: A Stringent Set Of 4662 Human Lincrnassupporting

confidence: 89%

“…In particular, recent studies suggested that some lincRNAs may act in cis and affect the gene expression of their chromosomal neighborhood (Ponjavic et al 2009;Orom et al 2010).…”

Section: Many Lincrnas Are Characterized By K4-k36 Domainsmentioning

confidence: 99%

Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses

Cabili¹,

Trapnell²,

Goff³

et al. 2011

View full text Add to dashboard Cite

show abstract

“…In agreement with signatures of conservation in mammalian lncRNAs (Ponjavic et al 2007(Ponjavic et al , 2009Guttman et al 2009Guttman et al , 2010Ørom et al 2010), a few lncRNAs were clearly conserved across fish species ( Fig. 4C; for two conserved examples, see Supplemental Fig.…”

Section: Genomic Characterization Of Embryonic Lncrnassupporting

confidence: 73%

“…Existing annotations of mammalian lncRNAs are derived from large-scale studies of cultured cells (Kapranov et al 2002;Rinn et al 2003;Carninci et al 2005;ENCODE Project Consortium et al 2007;Dinger et al 2008;Guttman et al 2009Guttman et al , 2010 or adult tissue samples (Ponjavic et al 2009;Cabili et al 2011). Such relatively homogenous and abundant samples have facilitated the identification of low abundance, cell type-specific transcripts.…”

mentioning

confidence: 99%

Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis

Pauli¹,

Valen²,

Lin³

et al. 2011

Genome Res.

726

815

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Long noncoding RNAs (lncRNAs) comprise a diverse class of transcripts that structurally resemble mRNAs but do not encode proteins. Recent genome-wide studies in humans and the mouse have annotated lncRNAs expressed in cell lines and adult tissues, but a systematic analysis of lncRNAs expressed during vertebrate embryogenesis has been elusive. To identify lncRNAs with potential functions in vertebrate embryogenesis, we performed a time-series of RNA-seq experiments at eight stages during early zebrafish development. We reconstructed 56,535 high-confidence transcripts in 28,912 loci, recovering the vast majority of expressed RefSeq transcripts while identifying thousands of novel isoforms and expressed loci. We defined a stringent set of 1133 noncoding multi-exonic transcripts expressed during embryogenesis. These include long intergenic ncRNAs (lincRNAs), intronic overlapping lncRNAs, exonic antisense overlapping lncRNAs, and precursors for small RNAs (sRNAs). Zebrafish lncRNAs share many of the characteristics of their mammalian counterparts: relatively short length, low exon number, low expression, and conservation levels comparable to that of introns. Subsets of lncRNAs carry chromatin signatures characteristic of genes with developmental functions. The temporal expression profile of lncRNAs revealed two novel properties: lncRNAs are expressed in narrower time windows than are protein-coding genes and are specifically enriched in early-stage embryos. In addition, several lncRNAs show tissue-specific expression and distinct subcellular localization patterns. Integrative computational analyses associated individual lncRNAs with specific pathways and functions, ranging from cell cycle regulation to morphogenesis. Our study provides the first systematic identification of lncRNAs in a vertebrate embryo and forms the foundation for future genetic, genomic, and evolutionary studies.

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“…Interestingly, compared to that in other organs, the highest number of expressed lncRNAs has been found in the brain, and their number surpasses that of the brain PCG transcripts 22, 23. The brain's lncRNAs have the highest tissue specificity and are the most evolutionarily conserved, with similar spatiotemporal expression patterns across multiple species 23, 24, 25…”

Section: Basic Characteristics and Functions Of Lncrnasmentioning

confidence: 99%

Long non‐coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma

Pop

Enciu

Necula

et al. 2018

J Cellular Molecular Medi

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Glioma biology is a major focus in tumour research, primarily due to the aggressiveness and high mortality rate of its most aggressive form, glioblastoma. Progress in understanding the molecular mechanisms behind poor prognosis of glioblastoma, regardless of treatment approaches, has changed the classification of brain tumours after nearly 100 years of relying on anatomopathological criteria. Expanding knowledge in genetic, epigenetic and translational medicine is also beginning to contribute to further elucidating molecular dysregulation in glioma. Long non‐coding RNAs (lncRNAs) and their main representatives, large intergenic non‐coding RNAs (lincRNAs), have recently been under scrutiny in glioma research, revealing novel mechanisms of pathogenesis and reinforcing others. Among those confirmed was the reactivation of events significant for foetal brain development and neuronal commitment. Novel mechanisms of tumour suppression and activation of stem‐like behaviour in tumour cells have also been examined. Interestingly, these processes involve lncRNAs that are present both during normal brain development and in brain malignancies and their reactivation might be explained by epigenetic mechanisms, which we discuss in detail in the present review. In addition, the review discusses the lncRNAs‐induced changes, as well as epigenetic changes that are consequential for tumour formation, affecting, in turn, the expression of various types of lncRNAs.

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Genomic and Transcriptional Co-Localization of Protein-Coding and Long Non-Coding RNA Pairs in the Developing Brain

Cited by 343 publications

References 58 publications

Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses

Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses

Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis

Long non‐coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma

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