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Functional consequences of developmentally regulated alternative splicing

Auinash Kalsotra, +1 more
- 01 Oct 2011 - 
- Vol. 12, Iss: 10, pp 715-729
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TLDR
Genome-wide analyses of metazoan transcriptomes have revealed an unexpected level of mRNA diversity that is generated by alternative splicing, which can drive determinative physiological change or have a permissive role by providing mRNA variability that is used by other regulatory mechanisms.
Abstract
Genome-wide analyses of metazoan transcriptomes have revealed an unexpected level of mRNA diversity that is generated by alternative splicing. Recently, regulatory networks have been identified through which splicing promotes dynamic remodelling of the transcriptome to promote physiological changes, which involve robust and coordinated alternative splicing transitions. The regulation of splicing in yeast, worms, flies and vertebrates affects a variety of biological processes. The functional classes of genes that are regulated by alternative splicing include both those with widespread homeostatic activities and those with cell-type-specific functions. Alternative splicing can drive determinative physiological change or can have a permissive role by providing mRNA variability that is used by other regulatory mechanisms.

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Circular RNAs are abundant, conserved, and associated with ALU repeats

TL;DR: High-throughput sequencing of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease showed that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.
Journal ArticleDOI

rMATS: Robust and flexible detection of differential alternative splicing from replicate RNA-Seq data

TL;DR: A new statistical model and computer program, replicate MATS (rMATS), designed for detection of differential alternative splicing from replicate RNA-Seq data, which uses a hierarchical model to simultaneously account for sampling uncertainty in individual replicates and variability among replicates.
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The RNA binding protein quaking regulates formation of circRNAs.

TL;DR: It is shown that hundreds of circRNAs are regulated during human epithelial-mesenchymal transition (EMT) and that the production of over one-third of abundant circ RNAs is dynamically regulated by the alternative splicing factor, Quaking (QKI), which itself is regulated during EMT.
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A census of human RNA-binding proteins.

TL;DR: This work presents a census of 1,542 manually curated RBPs that are analysed for their interactions with different classes of RNA, their evolutionary conservation, their abundance and their tissue-specific expression, a critical step towards the comprehensive characterization of proteins involved in human RNA metabolism.
Journal ArticleDOI

Sequencing depth and coverage: key considerations in genomic analyses

TL;DR: The issue of sequencing depth in the design of next-generation sequencing experiments is discussed and current guidelines and precedents on the issue of coverage are reviewed for four major study designs, including de novo genome sequencing, genome resequencing, transcriptome sequencing and genomic location analyses.
References
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Journal ArticleDOI

Alternative Isoform Regulation in Human Tissue Transcriptomes

TL;DR: An in-depth analysis of 15 diverse human tissue and cell line transcriptomes on the basis of deep sequencing of complementary DNA fragments yielding a digital inventory of gene and mRNA isoform expression suggested common involvement of specific factors in tissue-level regulation of both splicing and polyadenylation.
Journal ArticleDOI

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Journal ArticleDOI

Mdm2 promotes the rapid degradation of p53

TL;DR: It is proposed that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal.
Journal ArticleDOI

Complex networks orchestrate epithelial–mesenchymal transitions

TL;DR: Understanding how mesenchymal cells arise from an epithelial default status will also have a strong impact in unravelling the mechanisms that control fibrosis and cancer progression.
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