14 Facts About Alternative splicing


Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins.

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Biologically relevant alternative splicing occurs as a normal phenomenon in eukaryotes, where it increases the number of proteins that can be encoded by the genome.

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Mechanisms of alternative splicing are highly variable, and new examples are constantly being found, particularly through the use of high-throughput techniques.

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Abnormal variations in Alternative splicing are implicated in disease; a large proportion of human genetic disorders result from Alternative splicing variants.

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Abnormal Alternative splicing variants are thought to contribute to the development of cancer, and Alternative splicing factor genes are frequently mutated in different types of cancer.

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In 2021, it was discovered that the genome of adenovirus type 2, the adenovirus in which alternative splicing was first identified, was able to produce a much greater variety of mRNA than previously thought.

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The majority of Alternative splicing repressors are heterogeneous nuclear ribonucleoproteins such as hnRNPA1 and polypyrimidine tract binding protein .

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Genuine alternative splicing occurs in both protein-coding genes and non-coding genes to produce multiple products .

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Comparative studies indicate that alternative splicing preceded multicellularity in evolution, and suggest that this mechanism might have been co-opted to assist in the development of multicellular organisms.

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One study found that a relatively small percentage of alternative splicing variants were significantly higher in frequency in tumor cells than normal cells, suggesting that there is a limited set of genes which, when mis-spliced, contribute to tumor development.

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One example of a specific Alternative splicing variant associated with cancers is in one of the human DNMT genes.

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High-throughput approaches to investigate Alternative splicing have been developed, such as: DNA microarray-based analyses, RNA-binding assays, and deep sequencing.

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When combined with Alternative splicing assays, including in vivo reporter gene assays, the functional effects of polymorphisms or mutations on the Alternative splicing of pre-mRNA transcripts can then be analyzed.

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Use of reporter assays makes it possible to find the splicing proteins involved in a specific alternative splicing event by constructing reporter genes that will express one of two different fluorescent proteins depending on the splicing reaction that occurs.

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