Intron and Its Splicing Mechanism and Their Connection with Human Disease

In the maturation mechanism of a messenger RNA, splicing play an important role with removing the noncoding introns and ligating the coding exons. Alternative splicing (AS) gives an extra difficulty to this mechanism and to the regulation of gene expression. The possible disturbing in the alternative RNA splicing mechanism can be a reason to several diseases like cancers and neurodegenerative disorders. Intronless genes (IGs) are seen in almost 3% of the human genome. Functionality of IGs has an important role in signal transduction genes and related regulatory proteins. This diversity can be reason to IG-associated diseases, especially neuropathies, developmental disorders, and cancer. The retroelements can be seen in almost half of the human genome. The known informations indicate that insertion of retroelement into exons and introns of genes promote different types of genetic disease, including cancer. The retroelement connected mutagenesis cause to fifty different types of human disease. The molecular informations and bioinformatic analyses can be used to explain the connection with splicing mutations and genetic mechanisms of several different human disease and understanding of this mechanism play an important role in the formation of treatment programme against to these diseases.Bangladesh Journal of Medical Science Vol.15(3) 2016 p.307-312

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Defective control of pre–messenger RNA splicing in human disease

The Journal of Cell Biology ◽

10.1083/jcb.201510032 ◽

2016 ◽

Vol 212 (1) ◽

pp. 13-27 ◽

Cited By ~ 116

Author(s):

Benoit Chabot ◽

Lulzim Shkreta

Keyword(s):

Alternative Splicing ◽

Human Disease ◽

Rna Splicing ◽

Messenger Rna ◽

Recent Progress ◽

Rna Binding ◽

Rna Binding Proteins ◽

Regulatory Proteins ◽

Regulatory Sequence ◽

Sequence Elements

Examples of associations between human disease and defects in pre–messenger RNA splicing/alternative splicing are accumulating. Although many alterations are caused by mutations in splicing signals or regulatory sequence elements, recent studies have noted the disruptive impact of mutated generic spliceosome components and splicing regulatory proteins. This review highlights recent progress in our understanding of how the altered splicing function of RNA-binding proteins contributes to myelodysplastic syndromes, cancer, and neuropathologies.

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Evolutionary Perspective and Expression Analysis of Intronless Genes Highlight the Conservation of Their Regulatory Role

Frontiers in Genetics ◽

10.3389/fgene.2021.654256 ◽

2021 ◽

Vol 12 ◽

Author(s):

Katia Aviña-Padilla ◽

José Antonio Ramírez-Rafael ◽

Gabriel Emilio Herrera-Oropeza ◽

Vijaykumar Yogesh Muley ◽

Dulce I. Valdivia ◽

...

Keyword(s):

Rna Splicing ◽

Developmental Disorders ◽

Functional Divergence ◽

Wnt Signaling Pathway ◽

Control Of Gene Expression ◽

Embryonic Mouse ◽

Precise Control ◽

Regulatory Processes ◽

Intronless Genes ◽

Eukaryotic Genes

The structure of eukaryotic genes is generally a combination of exons interrupted by intragenic non-coding DNA regions (introns) removed by RNA splicing to generate the mature mRNA. A fraction of genes, however, comprise a single coding exon with introns in their untranslated regions or are intronless genes (IGs), lacking introns entirely. The latter code for essential proteins involved in development, growth, and cell proliferation and their expression has been proposed to be highly specialized for neuro-specific functions and linked to cancer, neuropathies, and developmental disorders. The abundant presence of introns in eukaryotic genomes is pivotal for the precise control of gene expression. Notwithstanding, IGs exempting splicing events entail a higher transcriptional fidelity, making them even more valuable for regulatory roles. This work aimed to infer the functional role and evolutionary history of IGs centered on the mouse genome. IGs consist of a subgroup of genes with one exon including coding genes, non-coding genes, and pseudogenes, which conform approximately 6% of a total of 21,527 genes. To understand their prevalence, biological relevance, and evolution, we identified and studied 1,116 IG functional proteins validating their differential expression in transcriptomic data of embryonic mouse telencephalon. Our results showed that overall expression levels of IGs are lower than those of MEGs. However, strongly up-regulated IGs include transcription factors (TFs) such as the class 3 of POU (HMG Box), Neurog1, Olig1, and BHLHe22, BHLHe23, among other essential genes including the β-cluster of protocadherins. Most striking was the finding that IG-encoded BHLH TFs fit the criteria to be classified as microproteins. Finally, predicted protein orthologs in other six genomes confirmed high conservation of IGs associated with regulating neural processes and with chromatin organization and epigenetic regulation in Vertebrata. Moreover, this study highlights that IGs are essential modulators of regulatory processes, such as the Wnt signaling pathway and biological processes as pivotal as sensory organ developing at a transcriptional and post-translational level. Overall, our results suggest that IG proteins have specialized, prevalent, and unique biological roles and that functional divergence between IGs and MEGs is likely to be the result of specific evolutionary constraints.

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Evolutionary Perspective and Expression Analysis of Intronless Genes Highlight the Conservation on Their Regulatory Role

10.1101/2021.01.13.426573 ◽

2021 ◽

Author(s):

Katia Aviña-Padilla ◽

José Antonio Ramírez-Rafael ◽

Gabriel Emilio Herrera-Oropeza ◽

Vijaykumar Muley ◽

Dulce I. Valdivia ◽

...

Keyword(s):

Gene Expression ◽

Rna Splicing ◽

Developmental Disorders ◽

Functional Divergence ◽

Wnt Signaling Pathway ◽

Early Embryo ◽

Control Of Gene Expression ◽

Precise Control ◽

Intronless Genes ◽

Eukaryotic Genes

AbstractEukaryotic gene structure is a combination of exons generally interrupted by intragenic non-coding DNA regions termed introns removed by RNA splicing to generate the mature mRNA. Thus, eukaryotic genes can be either single exon genes (SEGs) or multiple exon genes (MEGs). Among SEGs, intronless genes (IGs) are a subgroup that additionally lacks introns at their UTRs, and code for proteins essentially involved in development, growth, and cell proliferation. Gene expression of IGs has been proposed to be highly specialized for neuro-specific functions and linked to cancer, neuropathies, and developmental disorders. The abundant presence of introns in eukaryotic genomes is pivotal for the precise control of gene expression. Notwithstanding, IGs exempting splicing events entail a higher transcriptional fidelity, making them even more valuable for regulatory roles. This work aimed to infer the functional role and evolutionary history of IGs using the mouse genome. Intronless protein-coding genes consist of a subgroup of ~6 % of a total of 21,527 genes with one exon. To understand the prevalence, biological relevance, and evolution, we identified and studied their 1,116 functional proteins. We validated differential expression in transcriptomics data of early embryo stages using mouse telencephalon tissue. Our results showed that expression levels of IGs are lower compared to MEGs. However, strongly upregulated IGs include transcription factors (TFs) such as the class 3 of POU (HMG Box), Neurog1, Olig1, and BHLHe22, BHLHe23, among other essential genes including the beta cluster of protocadherins. Most striking was the finding that IG-encoded BHLH TFs qualify the criteria to be referred to as microprotein candidates. Finally, predicted protein orthologs in other six genomes confirmed a high conservancy of IGs associated with regulating neurobiological processes and with chromatin organization and epigenetic regulation in Vertebrata. Moreover, this study highlights that IGs are essential modulators of regulatory processes, as Wnt signaling pathway and biological processes as pivotal as sensory organs developing at a transcriptional and post-translational level. Overall, our results suggest that IG proteins have specialized, prevalent, and unique biological roles and that functional divergence between IGs and MEGs is likely to be the result of specific evolutionary constraints.

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Regulatory microRNAs in Brown, Brite and White Adipose Tissue

Cells ◽

10.3390/cells9112489 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2489

Author(s):

Seley Gharanei ◽

Kiran Shabir ◽

James E. Brown ◽

Martin O. Weickert ◽

Thomas M. Barber ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Messenger Rna ◽

Regulation Of Gene Expression ◽

Rna Degradation ◽

Comprehensive Overview ◽

Brown Adipocytes ◽

White Adipocytes ◽

Different Types ◽

Brown Adipogenesis

MicroRNAs (miRNAs) constitute a class of short noncoding RNAs which regulate gene expression by targeting messenger RNA, inducing translational repression and messenger RNA degradation. This regulation of gene expression by miRNAs in adipose tissue (AT) can impact on the regulation of metabolism and energy homeostasis, particularly considering the different types of adipocytes which exist in mammals, i.e., white adipocytes (white AT; WAT), brown adipocytes (brown AT; BAT), and inducible brown adipocytes in WAT (beige or brite or brown-in-white adipocytes). Indeed, an increasing number of miRNAs has been identified to regulate key signaling pathways of adipogenesis in BAT, brite AT, and WAT by acting on transcription factors that promote or inhibit adipocyte differentiation. For example, MiR-328, MiR-378, MiR-30b/c, MiR-455, MiR-32, and MiR-193b-365 activate brown adipogenesis, whereas MiR-34a, MiR-133, MiR-155, and MiR-27b are brown adipogenesis inhibitors. Given that WAT mainly stores energy as lipids, whilst BAT mainly dissipates energy as heat, clarifying the effects of miRNAs in different types of AT has recently attracted significant research interest, aiming to also develop novel miRNA-based therapies against obesity, diabetes, and other obesity-related diseases. Therefore, this review presents an up-to-date comprehensive overview of the role of key regulatory miRNAs in BAT, brite AT, and WAT.

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