Can alternative splicing change order of exons?
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| Papers (7) | Insight |
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| These results demonstrate that the coupling between alternative polyadenylation and alternative splicing is usually limited to defining the last exon. | |
146 Citations | At present, tandem exon duplication is the only mechanism of evolution of substitution alternative splicing that can be specifically demonstrated. |
72 Citations | This short sequence may participate in the control of splicing of exons carrying it, provided that they carry weak splice sites. |
77 Citations | Using molecular genetic tests, we first showed that the approximately 50-nt intronic flanking sequences of exons beyond the splice-site consensus are generally important for splicing. |
77 Citations | We conclude that most exons require signals in their immediate flanks for efficient splicing. |
| An alternative splicing regulation mechanism for exon 10 is postulated based on our experimental data and on published data. | |
| We revealed a mechanism that governs 3′ splice-site selection in these exons during alternative splicing. |
Related Questions
In wich mesure is the alteration of alternative splicing pathological for C9 ALS/FTD?5 answersThe alteration of alternative splicing (AS) in C9 ALS/FTD is a significant pathological feature with implications for disease progression. Studies have shown that in C9orf72-associated ALS/FTD, the GGGGCC repeat expansion leads to the sequestration of hnRNPH, resulting in insoluble aggregates and aberrant AS. This AS dysregulation extends to widespread intron retention affecting numerous transcripts, particularly those involved in cellular pathways crucial for disease etiology, such as proteasomal and autophagy systems. Furthermore, this splicing defect correlates with high insoluble TDP-43 levels and other disease-related RNA-binding proteins, indicating a common mechanism in C9 and sporadic ALS/FTD. These findings underscore the pathological impact of AS alterations in C9 ALS/FTD, highlighting the intricate interplay between RNA-binding proteins and splicing dysregulation in disease pathogenesis.
How does genome organization impact splicing?5 answersGenome organization significantly influences splicing processes. Nuclear speckles, specialized nuclear bodies, play a crucial role in mRNA splicing by affecting spliceosome concentrations and co-transcriptional splicing levels, demonstrating the impact of 3D spatial organization on splicing efficiency. Additionally, topologically associated domains (TADs) coordinate transcription and splicing kinetics, indicating that genomic compartments regulate RNA biogenesis and processing, including alternative splicing outcomes. Nucleotide composition bias, particularly GC-rich and AT-rich exons, influences exon recognition during splicing by interacting with specific splicing factors and affecting local chromatin organization, highlighting the direct link between genome organization and splicing regulation. Overall, the spatial organization of the genome plays a critical role in modulating splicing dynamics and efficiency.
How does alternative splicing play a role in cancer?4 answersAlternative splicing is a process that generates diverse proteins from a smaller number of genes. In cancer, aberrant splicing patterns are observed and can affect various aspects of cancer cell behavior, including growth, invasiveness, and metabolism. Driver oncogenes, such as mutant p53, CMYC, KRAS, and PI3K, can modify the alternative splicing landscape by regulating splicing factors and spliceosome components. Conversely, aberrant splicing can activate key oncogenes and pathways involved in tumor growth. Understanding the deregulation of splicing in cancer can aid in the development of improved diagnostic and treatment methods. Altered mRNA splicing in cancer can lead to the production of abnormal protein products that promote oncogenic transformation, metastasis, and chemotherapy resistance. Splicing imbalance in cancer is likely regulated by recurrent disruptions observed across different types of cancer. Identification of common and malignancy-specific splicing subtypes can provide insights into prognosis and potential therapeutic targets. Non-coding RNAs (ncRNAs) are also involved in alternative splicing regulation and abnormal expression of ncRNAs and ncRNA-related splicing events have been implicated in cancer initiation, progression, and therapy resistance. Targeting ncRNAs and AS-related factors may have therapeutic potential in cancer treatment. Alternative splicing events can generate different transcripts from the same gene, leading to structurally and functionally different proteins. Aberrant splicing plays a crucial role in tumor cells, affecting cancer progression, metastasis, and rapid proliferation. Alternative splicing events are linked to at least 15% of cancers and can serve as potential prognostic, diagnostic, and therapeutic biomarkers.
Are there any tissue specific alternative splicing events in DM1?5 answersTissue-specific alternative splicing events have been observed in DM1. In a study by Klinck et al., mis-splicing events were surveyed in DM1 tissues using a RT-PCR screening and validation platform. The results showed that DM1-associated splicing alterations were significantly enriched in cytoskeleton and channel genes, suggesting a role in muscle function. Additionally, Furling identified a mis-splicing event in DM1 muscles involving BIN1 exon11, which resulted in the expression of an inactive form of BIN1. This mis-splicing defect was found to contribute to muscle weakness in DM1. These findings indicate that tissue-specific alternative splicing events occur in DM1 and may play a role in the pathophysiology of the disease.
How does nanopore sequencing compare to other methods for detecting alternative splicing events?5 answersNanopore sequencing is a method that has advantages for detecting alternative splicing events. It records changes in electrical current when nucleic acid passes through a pore, allowing for the identification of splice junctions. Existing strategies for identifying splice junctions often rely on matched short-read data or annotated splice junctions, which can be expensive or limited to known annotations. However, nanopore sequencing can accurately identify splice junctions solely from nanopore data, providing numerous advantages. One method, NanoSplicer, uses raw nanopore signal to identify splice junctions by comparing observed squiggles to candidate squiggles representing potential junctions. This method improves splice junction identification, especially when the basecalling error rate near the splice junction is elevated. Another method, FLAME, is a bioinformatics pipeline that allows for comprehensive characterization of differentially spliced RNA transcripts using nanopore sequencing data. FLAME provides quantification of full-length splice variants, de novo recognition of splice sites and exons, and representation of exon connectivity. Overall, nanopore sequencing methods like NanoSplicer and FLAME offer accurate and reliable detection of alternative splicing events.
Does alternative splicing cut exons?4 answers