Table of Contents
How do you regulate alternative splicing?
Regulation of alternative splicing by DNA methylation can be mediated by proteins that directly recognize the modified nucleotide. Binding of the methyl-CpG-binding protein MeCP2 to exonic DNA regions promotes exon inclusion, most likely by recruiting HDACs and reducing RNAPII elongation [113].
Is alternative splicing gene regulation?
Alternative splicing is a crucial mechanism for gene regulation and for generating proteomic diversity. Recent estimates indicate that the expression of nearly 95% of human multi-exon genes involves alternative splicing1,2.
How does alternative splicing affect gene regulation?
Alternative splicing (AS) regulates gene expression patterns at the post-transcriptional level and generates a striking expansion of coding capacities of genomes and cellular protein diversity. RNA splicing could undergo modulation and close interaction with genetic and epigenetic machinery.
Is alternative splicing necessary?
Alternative splicing of precursor mRNA is an essential mechanism to increase the complexity of gene expression, and it plays an important role in cellular differentiation and organism development.
What is the consequence of alternative splicing of identical mRNA transcripts?
What is the consequence of alternative splicing of identical mRNA transcripts? A single gene can encode more than one kind of polypeptide, depending on which segments are treated as exons during RNA processing.
What is the consequence of alternative splicing?
The consequences of an alternative splicing are the deletion or the insertion of a nucleic acid sequence that might modify the protein sequence encoded by the gene.
What affects alternative splicing?
The inclusion or splicing of an alternative exon is therefore determined by combinatorial effects, cellular abundance, and competitive binding between SR activators and hnRNP inhibitors.
How is splicing regulated at the level of cis acting RNA sequence elements?
Alternative splicing is regulated by cis-acting elements within pre-mRNAs and trans-acting factors. The essential cis-acting elements are the 5′ splice site, the 3′ splice site, as well as the branchpoint sequence, which conform to partially conserved motifs that are recognized by cognate trans-acting factors [21].
What is the benefit of alternative splicing?
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.
What is alternative splicing and how does it occur?
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.
How does regulation of alternative splicing work?
Regulation of alternative splicing is a complicated process in which numerous interacting components are at work, including cis-acting elements and trans-acting factors, and is further guided by the functional coupling between transcription and splicing.
What is the history of alternative splicing?
Gilbert (1) first proposed the concept of alternative splicing in 1978, which is currently the mechanism that accounts for the discrepancy between the number of protein-coding genes (~25,000) in humans and the >90,000 different proteins that are actually generated (2, 3).
What is the difference between aberrant and stringent splicing?
Stringent regulation of alternative splicing is necessary for the functional requirements of complex tissues under normal conditions, whereas aberrant splicing appears to an underlying cause for an extremely high fraction of dysfunction and disease (68).
How many types of alternative splicing are there in vertebrates?
Systematic analyses of ESTs and microarray data have so far revealed seven main types of alternative splicing (12) (Fig. 1). The most prevalent pattern (~30%) is the cassette-type alternative exon (exon skipping) in vertebrates and invertebrates (Fig. 1C), while in lower metazoans, it is intron retention (Fig. 1F) (15).