When new exons are born

Sorek, Rotem

doi:10.1038/hdy.2009.62

Cited by 9 publications

(5 citation statements)

References 6 publications

(13 reference statements)

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“…Indeed, conserved exon/intron boundaries can be found immediately N-terminal and in close proximity to the C-terminal boundary of the CFC domain in the genomes of species ranging from Trichoplax to humans. It is therefore likely that the emergence of this domain was based on exon shuffling or an exonization of a preexisting intron, a process which can, for example, be triggered by intronic insertion of a retroelement providing novel splice acceptor motifs [22], [23]. Consistent with their ancient origins, the lengths of the positionally-conserved introns flanking the CFC vary widely from a few nucleotides to thousands of base pairs in LZT genes.…”

Section: Discussionmentioning

confidence: 99%

Evidence for Retrogene Origins of the Prion Gene Family

et al. 2011

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The evolutionary origin of prion genes, only known to exist in the vertebrate lineage, had remained elusive until recently. Following a lead from interactome investigations of the murine prion protein, our previous bioinformatic analyses revealed the evolutionary descent of prion genes from an ancestral ZIP metal ion transporter. However, the molecular mechanism of evolution remained unexplored. Here we present a computational investigation of this question based on sequence, intron-exon, synteny and pseudogene analyses. Our data suggest that during the emergence of metazoa, a cysteine-flanked core domain was modularly inserted, or arose de novo, in a preexisting ZIP ancestor gene to generate a prion-like ectodomain in a subbranch of ZIP genes. Approximately a half-billion years later, a genomic insertion of a spliced transcript coding for such a prion-like ZIP ectodomain may have created the prion founder gene. We document that similar genomic insertions involving ZIP transcripts, and probably relying on retropositional elements, have indeed occurred more than once throughout evolution.

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Section: Discussionmentioning

confidence: 99%

Evidence for Retrogene Origins of the Prion Gene Family

et al. 2011

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“…These provide non-canonical transcription factor binding sites and other regulatory sites that govern epigenetic modifications as well as provide cryptic splice sites that lead to alternative splicing or differential mRNA stability (5,(9)(10)(11)(12)(13)(14)(15). Alu-derived exons exhibit lineage specificity with high transcript inclusion levels and have relatively higher rates of evolution (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Multiple Alu exonizations in 3’UTR of a primate specific isoform of CYP20A1 creates a potential miRNA sponge

Bhattacharya

Jha

Singhal

et al. 2020

Preprint

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Background: Alu repeats contribute to phylogenetic novelties in conserved regulatory networks in primates. Exaptation of Alus in transcript isoforms could nucleate large-scale mRNA-miRNA interactions and modulate cellular outcomes. Result: Using a functional genomics approach, we report a transcript isoform of an orphan gene, CYP20A1 (CYP20A1_Alu-LT) that arise through exonization of 23 Alus in 3’UTR and is expressed in higher primates. CYP20A1_Alu-LT, confirmed by 3’RACE, is an outlier in length (9kb) and is expressed in multiple cell lines. Using publicly available datasets, we demonstrate its presence in single nucleus RNA-seq of 15928 human cortical neurons (including rosehip neurons). miRanda predicts ~4700 miRNA recognition elements (MREs; with threshold< -25kcal/mol) for ~1000 miRNAs, which have primarily originated within the 3’UTR-Alus post exonization. CYP20A1_Alu-LT could be a potential multi-miRNA sponge as it harbours ≥10 MREs for 140 miRNAs and has cytosolic localization. In order to test this further, we explored whether expression of CYP20A1_Alu-LT correlates with genome wide mRNAs harboring similar MRE targets. We carried out RNAseq with conjoint miRNA-seq analysis in primary human neurons as we observed CYP20A1_Alu-LT to be downregulated during heat shock response and upregulated in HIV1-Tat treatment. CYP20A1_Alu-LT expression was positively correlated with 380 genes that were significantly downregulated in heat shock and upregulated in Tat and harboured MREs for a set of nine expressed miRNAs that were also enriched in CYP20A1_Alu-LT. The enrichment of MREs in the 380 genes were significant compared to random sets of expressed (p=4.716e-12) as well as differentially expressed genes (p=8.134e-12). Gene ontology suggested involvement of these genes in neuronal development and hemostasis pathways. Conclusion: Our study suggests a potential role for CYP20A1_Alu-LT as miRNA sponge due to significant enrichment of MREs within Alus in a transcript isoform specific manner. This highlights a novel component of Alu-miRNA mediated transcriptional modulation that could govern specific physiological outcomes in higher primates.

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“…These provide non-canonical transcription factor binding sites and other regulatory sites that govern epigenetic modi cations as well as provide cryptic splice sites that lead to alternative splicing or differential mRNA stability (5,(9)(10)(11)(12)(13)(14)(15). Alu-derived exons exhibit lineage speci city with high transcript inclusion levels and have much higher rates of evolution (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Multiple Alu exonizations in 3’UTR of a primate specific isoform of CYP20A1 creates a potential miRNA sponge

Bhattacharya

Jha

Singhal

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Alu repeats contribute to phylogenetic novelties in conserved regulatory networks in primates. Exaptation of Alus in transcript isoforms could nucleate large-scale mRNA-miRNA interactions and modulate cellular outcomes. Result: Using a functional genomics approach, we report a transcript isoform of an orphan gene, CYP20A1 (CYP20A1_Alu-LT) that arise through exonization of 23 Alus in 3’UTR and is expressed in higher primates. CYP20A1_Alu-LT, confirmed by 3’RACE, is an outlier in length (9kb) and is expressed in multiple cell lines. We demonstrate its presence in single nucleus RNA-seq of ~16000 human cortical neurons (including rosehip neurons). Most strikingly, miRanda predicts ~4700 miRNA recognition elements (MREs; with threshold< -25kcal/mol) for ~1000 miRNAs, which have primarily originated within the 3’UTR-Alus post exonization. CYP20A1_Alu-LT could be a potential multi- miRNA sponge as it harbours - ≥10 MREs for 140 miRNAs and has cytosolic localization. In order to test this further, we explored whether expression of CYP20A1_Alu-LT correlates with genome wide mRNAs harboring similar MRE targets. We carried out RNAseq with conjoint miRNAseq analysis in primary human neurons as we observed CYP20A1_Alu-LT to be downregulated during heat shock response and upregulated in HIV1-Tat treatment. CYP20A1_Alu-LT expression was positively correlated with 380 genes that were significantly downregulated in heat shock and upregulated in Tat and harboured MREs for a set of nine expressed miRNAs that were also enriched in CYP20A1_Alu-LT. The enrichment of MREs in the 380 genes were significant compared to random sets of expressed (p=4.716e-12) as well as differentially expressed genes (p=8.134e-12). Gene ontology revealed involvement of these genes in neuronal development and hemostasis pathways. Conclusion: We demonstrate a potential role for CYP20A1_Alu-LT as miRNA sponge due to significant enrichment of MREs within Alus in a transcript isoform specific manner. This highlights a novel component of Alu-miRNA mediated transcriptional modulation that could govern specific physiological outcomes in higher primates.

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When new exons are born

Cited by 9 publications

References 6 publications

Evidence for Retrogene Origins of the Prion Gene Family

Evidence for Retrogene Origins of the Prion Gene Family

Multiple Alu exonizations in 3’UTR of a primate specific isoform of CYP20A1 creates a potential miRNA sponge

Multiple Alu exonizations in 3’UTR of a primate specific isoform of CYP20A1 creates a potential miRNA sponge

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