Asset Details
Do you wish to reserve the book?
RNA mis-splicing in disease
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
RNA mis-splicing in disease
Do you wish to request the book?
RNA mis-splicing in disease
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
RNA mis-splicing in disease
2016
Overview
Key Points
The human transcriptome is the product of a coordinated series of transcriptional, co-transcriptional and post-transcriptional regulatory events.
RNA splicing is a key regulatory step in gene expression that allows a limited genome to express an impressive diversity of coding and non-coding RNAs.
RNA mis-splicing causes a large array of human diseases due to hereditary and somatic mutations.
Mis-splicing may result from mutations to RNA
cis
-regulatory elements, core spliceosomal components or
trans
-acting regulatory factors.
Mutations in some genes, such as lamin A (
LMNA
), cause multiple types of diseases, from muscular dystrophy to premature ageing syndromes.
A key small nuclear RNA (snRNA) component of the minor spliceosome functions as a stress-activated switch to control expression levels of genes containing minor introns.
Some splicing factors linked to diseases, such as amyotrophic lateral sclerosis, contain low-complexity regions with prion-like domains that are susceptible to abnormal aggregation.
Splicing modulatory therapeutic strategies have been developed that target a range of diseases, including muscular dystrophies and motor neuron diseases, and are currently being tested in clinical trials.
Complex and intricate RNA splicing mechanisms are crucial for gene regulation and for maximizing proteomic diversity. This Review discusses how alterations to splicing mechanisms — such as mutations in pre-mRNAs, or mutations and dysregulation of core spliceosome proteins and other RNA-binding proteins — results in diverse molecular consequences and various diseases. Opportunities for therapeutic correction of these defects are also explored.
The human transcriptome is composed of a vast RNA population that undergoes further diversification by splicing. Detecting specific splice sites in this large sequence pool is the responsibility of the major and minor spliceosomes in collaboration with numerous splicing factors. This complexity makes splicing susceptible to sequence polymorphisms and deleterious mutations. Indeed, RNA mis-splicing underlies a growing number of human diseases with substantial societal consequences. Here, we provide an overview of RNA splicing mechanisms followed by a discussion of disease-associated errors, with an emphasis on recently described mutations that have provided new insights into splicing regulation. We also discuss emerging strategies for splicing-modulating therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group
