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Differential fates of introns in gene expression due to global alternative splicing
The discovery of introns over four decades ago revealed a new vision of genes and their interrupted arrangement. Throughout the years, it has appeared that introns play essential roles in the regulation of gene expression. Unique processing of excised introns through the formation of lariats suggest...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758631/ https://www.ncbi.nlm.nih.gov/pubmed/34907472 http://dx.doi.org/10.1007/s00439-021-02409-6 |
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author | Kumari, Anjani Sedehizadeh, Saam Brook, John David Kozlowski, Piotr Wojciechowska, Marzena |
author_facet | Kumari, Anjani Sedehizadeh, Saam Brook, John David Kozlowski, Piotr Wojciechowska, Marzena |
author_sort | Kumari, Anjani |
collection | PubMed |
description | The discovery of introns over four decades ago revealed a new vision of genes and their interrupted arrangement. Throughout the years, it has appeared that introns play essential roles in the regulation of gene expression. Unique processing of excised introns through the formation of lariats suggests a widespread role for these molecules in the structure and function of cells. In addition to rapid destruction, these lariats may linger on in the nucleus or may even be exported to the cytoplasm, where they remain stable circular RNAs (circRNAs). Alternative splicing (AS) is a source of diversity in mature transcripts harboring retained introns (RI-mRNAs). Such RNAs may contain one or more entire retained intron(s) (RIs), but they may also have intron fragments resulting from sequential excision of smaller subfragments via recursive splicing (RS), which is characteristic of long introns. There are many potential fates of RI-mRNAs, including their downregulation via nuclear and cytoplasmic surveillance systems and the generation of new protein isoforms with potentially different functions. Various reports have linked the presence of such unprocessed transcripts in mammals to important roles in normal development and in disease-related conditions. In certain human neurological-neuromuscular disorders, including myotonic dystrophy type 2 (DM2), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and Duchenne muscular dystrophy (DMD), peculiar processing of long introns has been identified and is associated with their pathogenic effects. In this review, we discuss different mechanisms involved in the processing of introns during AS and the functions of these large sections of the genome in our biology. |
format | Online Article Text |
id | pubmed-8758631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-87586312022-01-26 Differential fates of introns in gene expression due to global alternative splicing Kumari, Anjani Sedehizadeh, Saam Brook, John David Kozlowski, Piotr Wojciechowska, Marzena Hum Genet Review The discovery of introns over four decades ago revealed a new vision of genes and their interrupted arrangement. Throughout the years, it has appeared that introns play essential roles in the regulation of gene expression. Unique processing of excised introns through the formation of lariats suggests a widespread role for these molecules in the structure and function of cells. In addition to rapid destruction, these lariats may linger on in the nucleus or may even be exported to the cytoplasm, where they remain stable circular RNAs (circRNAs). Alternative splicing (AS) is a source of diversity in mature transcripts harboring retained introns (RI-mRNAs). Such RNAs may contain one or more entire retained intron(s) (RIs), but they may also have intron fragments resulting from sequential excision of smaller subfragments via recursive splicing (RS), which is characteristic of long introns. There are many potential fates of RI-mRNAs, including their downregulation via nuclear and cytoplasmic surveillance systems and the generation of new protein isoforms with potentially different functions. Various reports have linked the presence of such unprocessed transcripts in mammals to important roles in normal development and in disease-related conditions. In certain human neurological-neuromuscular disorders, including myotonic dystrophy type 2 (DM2), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and Duchenne muscular dystrophy (DMD), peculiar processing of long introns has been identified and is associated with their pathogenic effects. In this review, we discuss different mechanisms involved in the processing of introns during AS and the functions of these large sections of the genome in our biology. Springer Berlin Heidelberg 2021-12-14 2022 /pmc/articles/PMC8758631/ /pubmed/34907472 http://dx.doi.org/10.1007/s00439-021-02409-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Kumari, Anjani Sedehizadeh, Saam Brook, John David Kozlowski, Piotr Wojciechowska, Marzena Differential fates of introns in gene expression due to global alternative splicing |
title | Differential fates of introns in gene expression due to global alternative splicing |
title_full | Differential fates of introns in gene expression due to global alternative splicing |
title_fullStr | Differential fates of introns in gene expression due to global alternative splicing |
title_full_unstemmed | Differential fates of introns in gene expression due to global alternative splicing |
title_short | Differential fates of introns in gene expression due to global alternative splicing |
title_sort | differential fates of introns in gene expression due to global alternative splicing |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758631/ https://www.ncbi.nlm.nih.gov/pubmed/34907472 http://dx.doi.org/10.1007/s00439-021-02409-6 |
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