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Isoform Age - Splice Isoform Profiling Using Long-Read Technologies
Alternative splicing (AS) of RNA is a key mechanism that results in the expression of multiple transcript isoforms from single genes and leads to an increase in the complexity of both the transcriptome and proteome. Regulation of AS is critical for the correct functioning of many biological pathways...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364947/ https://www.ncbi.nlm.nih.gov/pubmed/34409069 http://dx.doi.org/10.3389/fmolb.2021.711733 |
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author | De Paoli-Iseppi, Ricardo Gleeson, Josie Clark, Michael B. |
author_facet | De Paoli-Iseppi, Ricardo Gleeson, Josie Clark, Michael B. |
author_sort | De Paoli-Iseppi, Ricardo |
collection | PubMed |
description | Alternative splicing (AS) of RNA is a key mechanism that results in the expression of multiple transcript isoforms from single genes and leads to an increase in the complexity of both the transcriptome and proteome. Regulation of AS is critical for the correct functioning of many biological pathways, while disruption of AS can be directly pathogenic in diseases such as cancer or cause risk for complex disorders. Current short-read sequencing technologies achieve high read depth but are limited in their ability to resolve complex isoforms. In this review we examine how long-read sequencing (LRS) technologies can address this challenge by covering the entire RNA sequence in a single read and thereby distinguish isoform changes that could impact RNA regulation or protein function. Coupling LRS with technologies such as single cell sequencing, targeted sequencing and spatial transcriptomics is producing a rapidly expanding suite of technological approaches to profile alternative splicing at the isoform level with unprecedented detail. In addition, integrating LRS with genotype now allows the impact of genetic variation on isoform expression to be determined. Recent results demonstrate the potential of these techniques to elucidate the landscape of splicing, including in tissues such as the brain where AS is particularly prevalent. Finally, we also discuss how AS can impact protein function, potentially leading to novel therapeutic targets for a range of diseases. |
format | Online Article Text |
id | pubmed-8364947 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83649472021-08-17 Isoform Age - Splice Isoform Profiling Using Long-Read Technologies De Paoli-Iseppi, Ricardo Gleeson, Josie Clark, Michael B. Front Mol Biosci Molecular Biosciences Alternative splicing (AS) of RNA is a key mechanism that results in the expression of multiple transcript isoforms from single genes and leads to an increase in the complexity of both the transcriptome and proteome. Regulation of AS is critical for the correct functioning of many biological pathways, while disruption of AS can be directly pathogenic in diseases such as cancer or cause risk for complex disorders. Current short-read sequencing technologies achieve high read depth but are limited in their ability to resolve complex isoforms. In this review we examine how long-read sequencing (LRS) technologies can address this challenge by covering the entire RNA sequence in a single read and thereby distinguish isoform changes that could impact RNA regulation or protein function. Coupling LRS with technologies such as single cell sequencing, targeted sequencing and spatial transcriptomics is producing a rapidly expanding suite of technological approaches to profile alternative splicing at the isoform level with unprecedented detail. In addition, integrating LRS with genotype now allows the impact of genetic variation on isoform expression to be determined. Recent results demonstrate the potential of these techniques to elucidate the landscape of splicing, including in tissues such as the brain where AS is particularly prevalent. Finally, we also discuss how AS can impact protein function, potentially leading to novel therapeutic targets for a range of diseases. Frontiers Media S.A. 2021-08-02 /pmc/articles/PMC8364947/ /pubmed/34409069 http://dx.doi.org/10.3389/fmolb.2021.711733 Text en Copyright © 2021 De Paoli-Iseppi, Gleeson and Clark. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences De Paoli-Iseppi, Ricardo Gleeson, Josie Clark, Michael B. Isoform Age - Splice Isoform Profiling Using Long-Read Technologies |
title | Isoform Age - Splice Isoform Profiling Using Long-Read Technologies |
title_full | Isoform Age - Splice Isoform Profiling Using Long-Read Technologies |
title_fullStr | Isoform Age - Splice Isoform Profiling Using Long-Read Technologies |
title_full_unstemmed | Isoform Age - Splice Isoform Profiling Using Long-Read Technologies |
title_short | Isoform Age - Splice Isoform Profiling Using Long-Read Technologies |
title_sort | isoform age - splice isoform profiling using long-read technologies |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364947/ https://www.ncbi.nlm.nih.gov/pubmed/34409069 http://dx.doi.org/10.3389/fmolb.2021.711733 |
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