Definition of an isoform switching?
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4.4 years ago
a4appy23 ▴ 50

im from non genetics background who started taking a course in genetics.So i was wondering what is an gene isoform switching? what happens when there is an isoform switching .can some one explain it in layman terms.

gene rna-seq genome sequencing • 3.7k views
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4.4 years ago

A single eukaryotic gene can give rise to different messenger RNA transcripts (mRNA) which are called gene isoform. Alternative splicing signal, usage of different alternative transcriptional start site and transcriptional termination site are the molecular phenomena that can give rise to different isoform of a single gene . Different isoforms of a single gene functions differently. Eukaryotic cells can decide, depending on their need and regulatory signal, which isoform to express and can switch from expressing one isoform to another. This is called gene isoform switching. Gene isoform switching is predominant phenomena during mammalian development and in various disease conditions like cancer. Alternative splicing can give rise to different mRNA isoforms from a single gene that are distinct in their exonic and intronic sequence composition. Usage of alternative transcriptional start site can lead to generate mRNA transcript isoforms that are different in 5' leader sequence. Alternative termination site selection promotes in expressing mRNA isoforms that differs in 3' end sequence.

Hope you got the answer. Ref.: The Landscape of Isoform Switches in Human Cancers Kristoffer Vitting-Seerup and Albin Sandelin, Molecular Cancer Research June, 2017

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Great answer (I have to say that since I'm the author of the refrence :D). Just want to add that the more I work with this field the more I find that isoform switches occurs in all biological systems/comparisons. Compare different tissues or cell types - then they use different isoforms, compare different cell states and they use different isoforms etc.

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4.4 years ago
b.bearmi ▴ 10

In eukaryotes, genes don't have a continuous open reading frame, from start to stop codons, instead, they have exons (protein-coding bits) and introns (non-coding bits). After mRNA is transcribed, introns are spliced out of it. Cut sites on the initial mRNA are called splice sites. Some genes will have more than one pattern of splicing - meaning some splice sites would be used alternatively, and the resulting mRNA (and therefore, protein) would have a slightly different sequence - those would be different isoforms of the same gene (or rather, of the same transcript). There, you have isoform switching, also called alternative splicing: a regulated switch from one isoform to another.

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Just a small addition: As well as alternative splicing isoform switches is also the result of alternative transcription start and termination sites - and the changes can be quite large.

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