A unified framework of overlapping genes: Towards the origination and endogenic regulation

Ho, Meng‐Ru; Tsai, Kuo‐Wang; Lin, Wen-chang

doi:10.1016/j.ygeno.2012.06.011

Cited by 23 publications

(30 citation statements)

References 52 publications

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“…Expression correlation is a predominant characteristic of overlapping genes89 and overlapping configurations, local genomic environment and the evolutionary age of genes are important factors influencing this correlation. SEB pairs, under common regulatory system, showed the highest expression correlation and H2H pairs had higher correlation than other different-strand overlaps.…”

Section: Discussionmentioning

confidence: 99%

“…A mutation in overlapping region may disrupt the function of the two genes simultaneously. Nevertheless, overlapping genes do not show higher sequence conservation compared with non-overlapping genes and the overlap structure are poorly preserved during evolution81011.…”

mentioning

confidence: 99%

“…Aside from contracting genome size, overlaps have been hypothesized to be involved in regulating gene expression at diverse levels, including transcription, mRNA splicing, transport, processing, stability and translation456. The transcription of antisense genes affects both the splicing and the expression of sense genes in human7 and the expression of overlapping genes are highly correlated89. A mutation in overlapping region may disrupt the function of the two genes simultaneously.…”

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confidence: 99%

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The Evolution and Expression Pattern of Human Overlapping lncRNA and Protein-coding Gene Pairs

Ning

Wang

et al. 2017

Sci Rep

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Long non-coding RNA overlapping with protein-coding gene (lncRNA-coding pair) is a special type of overlapping genes. Protein-coding overlapping genes have been well studied and increasing attention has been paid to lncRNAs. By studying lncRNA-coding pairs in human genome, we showed that lncRNA-coding pairs were more likely to be generated by overprinting and retaining genes in lncRNA-coding pairs were given higher priority than non-overlapping genes. Besides, the preference of overlapping configurations preserved during evolution was based on the origin of lncRNA-coding pairs. Further investigations showed that lncRNAs promoting the splicing of their embedded protein-coding partners was a unilateral interaction, but the existence of overlapping partners improving the gene expression was bidirectional and the effect was decreased with the increased evolutionary age of genes. Additionally, the expression of lncRNA-coding pairs showed an overall positive correlation and the expression correlation was associated with their overlapping configurations, local genomic environment and evolutionary age of genes. Comparison of the expression correlation of lncRNA-coding pairs between normal and cancer samples found that the lineage-specific pairs including old protein-coding genes may play an important role in tumorigenesis. This work presents a systematically comprehensive understanding of the evolution and the expression pattern of human lncRNA-coding pairs.

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Section: Discussionmentioning

confidence: 99%

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The Evolution and Expression Pattern of Human Overlapping lncRNA and Protein-coding Gene Pairs

Ning

Wang

et al. 2017

Sci Rep

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“…The functional role of this putative RCAN1 NAT suggests the possible existence of a complex fine-tuning regulation of NAT and RCAN genes. Furthermore, the overlapping nucleotide sequences observed between the first exon of RCAN genes, at least for RCAN2 and RCAN3 , and NATs suggest the possibility that the gene expression regulation of both NAT and RCAN genes is carried out by a bidirectional promoter [88]. Interestingly, this bidirectional promoter is in close proximity or overlapping with the CpG island of the RCAN gene, a feature characteristic of bidirectional promoters [89].…”

Section: Discussionmentioning

confidence: 99%

The Vertebrate RCAN Gene Family: Novel Insights into Evolution, Structure and Regulation

et al. 2014

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Recently there has been much interest in the Regulators of Calcineurin (RCAN) proteins which are important endogenous modulators of the calcineurin-NFATc signalling pathway. They have been shown to have a crucial role in cellular programmes such as the immune response, muscle fibre remodelling and memory, but also in pathological processes such as cardiac hypertrophy and neurodegenerative diseases. In vertebrates, the RCAN family form a functional subfamily of three members RCAN1, RCAN2 and RCAN3 whereas only one RCAN is present in the rest of Eukarya. In addition, RCAN genes have been shown to collocate with RUNX and CLIC genes in ACD clusters (ACD21, ACD6 and ACD1). How the RCAN genes and their clustering in ACDs evolved is still unknown. After analysing RCAN gene family evolution using bioinformatic tools, we propose that the three RCAN vertebrate genes within the ACD clusters, which evolved from single copy genes present in invertebrates and lower eukaryotes, are the result of two rounds of whole genome duplication, followed by a segmental duplication. This evolutionary scenario involves the loss or gain of some RCAN genes during evolution. In addition, we have analysed RCAN gene structure and identified the existence of several characteristic features that can be involved in RCAN evolution and gene expression regulation. These included: several transposable elements, CpG islands in the 5′ region of the genes, the existence of antisense transcripts (NAT) associated with the three human genes, and considerable evidence for bidirectional promoters that regulate RCAN gene expression. Furthermore, we show that the CpG island associated with the RCAN3 gene promoter is unmethylated and transcriptionally active. All these results provide timely new insights into the molecular mechanisms underlying RCAN function and a more in depth knowledge of this gene family whose members are obvious candidates for the development of future therapies.

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“…Nested genes represent a subgroup of overlapping genes [12]: one gene (“nested”) is situated totally inside another gene (“host”). Nearly all protein-coding nested genes are thought to have emerged by insertion of a corresponding DNA sequence into an intron of a pre-existing gene [13].…”

Section: Introductionmentioning

confidence: 99%

Origin and Loss of Nested LRRTM/α-Catenin Genes during Vertebrate Evolution

2014

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Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) form in mammals a family of four postsynaptic adhesion proteins, which have been shown to bind neurexins and heparan sulphate proteoglycan (HSPG) glypican on the presynaptic side. Mutations in the genes encoding LRRTMs and neurexins are implicated in human cognitive disorders such as schizophrenia and autism. Our analysis shows that in most jawed vertebrates, lrrtm1, lrrtm2, and lrrtm3 genes are nested on opposite strands of large conserved intron of α-catenin genes ctnna2, ctnna1, and ctnna3, respectively. No lrrtm genes could be found in tunicates or lancelets, while two lrrtm genes are found in the lamprey genome, one of which is adjacent to a single ctnna homolog. Based on similar highly positive net charge of lamprey LRRTMs and the HSPG-binding LRRTM3 and LRRTM4 proteins, we speculate that the ancestral LRRTM might have bound HSPG before acquiring neurexins as binding partners. Our model suggests that lrrtm gene translocated into the large ctnna intron in early vertebrates, and that subsequent duplications resulted in three lrrtm/ctnna gene pairs present in most jawed vertebrates. However, we detected three prominent exceptions: (1) the lrrtm3/ctnna3 gene structure is absent in the ray-finned fish genomes, (2) the genomes of clawed frogs contain ctnna1 but lack the corresponding nested (lrrtm2) gene, and (3) contain lrrtm3 gene in the syntenic position but lack the corresponding host (ctnna3) gene. We identified several other protein-coding nested gene structures of which either the host or the nested gene has presumably been lost in the frog or chicken lineages. Interestingly, majority of these nested genes comprise LRR domains.

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A unified framework of overlapping genes: Towards the origination and endogenic regulation

Cited by 23 publications

References 52 publications

The Evolution and Expression Pattern of Human Overlapping lncRNA and Protein-coding Gene Pairs

The Evolution and Expression Pattern of Human Overlapping lncRNA and Protein-coding Gene Pairs

The Vertebrate RCAN Gene Family: Novel Insights into Evolution, Structure and Regulation

Origin and Loss of Nested LRRTM/α-Catenin Genes during Vertebrate Evolution

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