What can be affected by splicing?
The splicing mutation may occur in both introns and exons and disrupt existing splice sites, create new ones, or activate the cryptic ones. They also can influence splicing enhancers and silencers binding or alter the secondary structure of messenger RNA and therefore prevent the binding of the spliceosome elements.
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 kind of mutations might lead to splicing errors?
What kinds of mutations might lead to splicing errors? Think of different possible outcomes if splicing errors occur. Mutations in the spliceosome recognition sequence at each end of the intron, or in the proteins and RNAs that make up the spliceosome, may impair splicing.
How does splicing affect gene expression?
Abstract. Alternative splicing of RNA is a crucial process for changing the genomic instructions into functional proteins. It plays a critical role in the regulation of gene expression and protein diversity in a variety of eukaryotes. In humans, approximately 95% of multi-exon genes undergo alternative splicing.
What happens if splicing does not occur?
Not only do the introns not carry information to build a protein, they actually have to be removed in order for the mRNA to encode a protein with the right sequence. If the spliceosome fails to remove an intron, an mRNA with extra “junk” in it will be made, and a wrong protein will get produced during translation.
Does deletion affect splicing?
We find that, consistent with our predictions, longer deletions affect splicing at a much higher rate compared to insertions and short deletions. We also explore other potential constraints in introns and show that most of these also disproportionately affect large deletions.
What is gene splicing used for?
Thus, gene splicing enables a single gene to increase its coding capacity, allowing the synthesis of protein isoforms that are structurally and functionally distinct. Gene splicing is observed in high proportion of genes. In human cells, about 40-60% of the genes are known to exhibit alternative splicing.
Are there any diseases caused by mutations in splicing factors?
There are only a few reports of mutations in core elements of the splicing machinery that result in human diseases. For example, autosomal dominant forms of retinitis pigmentosa is caused by mutation in the splicing factors PRPF31/U4-61k [9], [10] and PRP8 [11].
How does alternative splicing affect the human genome?
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.
Where does the mutation occur in intron splicing?
The mutation must occur at the specific site at which intron splicing occurs: within non-coding sites in a gene, directly next to the location of the exon. The mutation can be an insertion, deletion, frameshift, etc.
How does the Human Splicing Finder database work?
The Human Splicing Finder is an online database stemming from the Human Genome Project data. The genome database identifies thousands of mutations related to medical and health fields, as well as providing critical research information regarding splice site mutations.
