Introns as Gene Regulators: A Brick on the Accelerator

A picture is beginning to emerge from a variety of organisms that for a subset of genes, the most important sequences that regulate expression are situated not in the promoter but rather are located within introns in the first kilobase of transcribed sequences. The actual sequences involved are diff...

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Main Author: Alan B. Rose
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-02-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2018.00672/full
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author Alan B. Rose
author_facet Alan B. Rose
author_sort Alan B. Rose
collection DOAJ
description A picture is beginning to emerge from a variety of organisms that for a subset of genes, the most important sequences that regulate expression are situated not in the promoter but rather are located within introns in the first kilobase of transcribed sequences. The actual sequences involved are difficult to identify either by sequence comparisons or by deletion analysis because they are dispersed, additive, and poorly conserved. However, expression-controlling introns can be identified computationally in species with relatively small introns, based on genome-wide differences in oligomer composition between promoter-proximal and distal introns. The genes regulated by introns are often expressed in most tissues and are among the most highly expressed in the genome. The ability of some introns to strongly stimulate mRNA accumulation from several hundred nucleotides downstream of the transcription start site, even when the promoter has been deleted, reveals that our understanding of gene expression remains incomplete. It is unlikely that any diseases are caused by point mutations or small deletions that reduce the expression of an intron-regulated gene unless splicing is also affected. However, introns may be particularly useful in practical applications such as gene therapy because they strongly activate expression but only affect the transcription unit in which they are located.
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spelling doaj.art-1e6c0c17696f4d6ea626258f403b84292022-12-21T19:54:18ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-02-01910.3389/fgene.2018.00672427806Introns as Gene Regulators: A Brick on the AcceleratorAlan B. RoseA picture is beginning to emerge from a variety of organisms that for a subset of genes, the most important sequences that regulate expression are situated not in the promoter but rather are located within introns in the first kilobase of transcribed sequences. The actual sequences involved are difficult to identify either by sequence comparisons or by deletion analysis because they are dispersed, additive, and poorly conserved. However, expression-controlling introns can be identified computationally in species with relatively small introns, based on genome-wide differences in oligomer composition between promoter-proximal and distal introns. The genes regulated by introns are often expressed in most tissues and are among the most highly expressed in the genome. The ability of some introns to strongly stimulate mRNA accumulation from several hundred nucleotides downstream of the transcription start site, even when the promoter has been deleted, reveals that our understanding of gene expression remains incomplete. It is unlikely that any diseases are caused by point mutations or small deletions that reduce the expression of an intron-regulated gene unless splicing is also affected. However, introns may be particularly useful in practical applications such as gene therapy because they strongly activate expression but only affect the transcription unit in which they are located.https://www.frontiersin.org/article/10.3389/fgene.2018.00672/fullintrongene expressiontranscriptiongene regulationpromoterintron-mediated enhancement
spellingShingle Alan B. Rose
Introns as Gene Regulators: A Brick on the Accelerator
Frontiers in Genetics
intron
gene expression
transcription
gene regulation
promoter
intron-mediated enhancement
title Introns as Gene Regulators: A Brick on the Accelerator
title_full Introns as Gene Regulators: A Brick on the Accelerator
title_fullStr Introns as Gene Regulators: A Brick on the Accelerator
title_full_unstemmed Introns as Gene Regulators: A Brick on the Accelerator
title_short Introns as Gene Regulators: A Brick on the Accelerator
title_sort introns as gene regulators a brick on the accelerator
topic intron
gene expression
transcription
gene regulation
promoter
intron-mediated enhancement
url https://www.frontiersin.org/article/10.3389/fgene.2018.00672/full
work_keys_str_mv AT alanbrose intronsasgeneregulatorsabrickontheaccelerator