Can alternative splicing cause disease?
By Mia Lopez
Can alternative splicing cause disease?
Alternative splicing is a key element in eukaryotic gene expression that increases the coding capacity of the human genome and an increasing number of examples illustrates that the selection of wrong splice sites causes human disease. A fine-tuned balance of factors regulates splice site selection.
How is alternative splicing regulated?
Splicing is regulated by trans-acting proteins (repressors and activators) and corresponding cis-acting regulatory sites (silencers and enhancers) on the pre-mRNA. However, as part of the complexity of alternative splicing, it is noted that the effects of a splicing factor are frequently position-dependent.
Does alternative splicing cause cancer?
Alternative splicing plays a significant role in cancer, allowing the malignant progression of initiated tumor cells and contributing specifically to tumor progression. In this article, we reviewed alternative splicing in relation to the hallmarks of cancer cells.
Why is alternative splicing important in development and disease?
Alternative splicing expands proteome complexity by generating multiple transcript (and protein) isoforms from a single gene. Numerous alternative splicing events occur during cell differentiation and tissue maturation, suggesting that alternative splicing supports proper development.
What causes incorrect splicing?
Several genetic diseases may be the result of splice site mutations. For example, mutations that cause the incorrect splicing of β-globin mRNA are responsible of some cases of β-thalassemia. Another Example is TTP (thrombotic thrombocytopenic purpura). TTP is caused by deficiency of ADAMTS-13.
What does alternative splicing allow for?
The overall function of alternative splicing is to increase the diversity of mRNAs expressed from the genome. Experimental analysis of these protein isoforms showed that alternative splicing regulates binding between proteins, between proteins and nucleic acids as well as between proteins and membranes.
What is the advantage of alternative splicing?
Alternative splicing affords a significant evolutionary advantage by providing a large source of proteomic diversity. Alternative splicing is often regulated at the tissue level, and tissue-specific variants cooperate to modulate protein–protein interaction networks.
What happens during alternative splicing?
Abstract. Alternative splicing is the process of selecting different combinations of splice sites within a messenger RNA precursor (pre-mRNA) to produce variably spliced mRNAs. These multiple mRNAs can encode proteins that vary in their sequence and activity, and yet arise from a single gene.
What is the benefit from alternative splicing during mRNA processing?
The overall function of alternative splicing is to increase the diversity of the mRNA expressed from the genome. Due to the combinatorial control mechanisms that regulate alternative exon recognition, splicing programs coordinate the generation of mRNA isoforms from multiple genes.
