RNA Alternative Splicing
First let us understand what splicing is. DNA directs the synthesis or production of RNA. This is called transcription. The RNA so formed may then undergo modification. This is called splicing. In the process of splicing, exons are joined and introns are removed. Exons, incidentally, are coding nucleic acid sequences found in DNA and in mature RNA molecules like mRNA, rRNA or tRNA. Introns are non-coding DNA parts that help form immature or precursor mRNA and also some non-coding RNA; introns are removed during the creation of mature RNA and do not form proteins.
In RNA alternative splicing, exons are joined in many different ways and give rise to many different mRNAs. These then help form many different types of proteins. So, in brief, a single gene, by the process of RNA alternative splicing, is able to encode a number of different proteins. If you think about it, producing diverse proteins from one gene is more efficient and economical than having to produce those diverse proteins from diverse genes. Another favorable point is that if a gene happens to mutate, it can give rise to a new protein by excluding or including exons, without affecting the original protein.
The production of alternatively spliced mRNAs is regulated by a system of intermolecular or transacting proteins like splicing activators (which promote splice site use) and splicing repressors (which reduce splice site use), that bind intermolecular or cis-acting sites on the mRNA.
There are different modes of RNA alternative splicing, the main ones being -
- Exon skipping
- Mutually exclusive exon splicing
- Alternative donor sites
- Alternative splice acceptor sites
- Intron retention
- Multiple promoters
- Multiple polyadenylation sites
Importance of RNA Alternative Splicing
RNA alternative splicing enables genetic efficiency and genetic diversity. On the negative side, abnormally spliced mRNA may contribute to a host of genetic disorders, including cancer.
According to researchers, RNA alternative splicing probably first occurred in the earliest single cell life forms and played a role in the evolution of multicellular life forms. It is commonly seen in all eukaryotes, that is, organisms with complex, membrane-enclosed cellular structures. In studying and comparing the genomes of vertebrates and invertebrates, researchers found a good bit of difference in the rates of alternative splicing in vertebrates and non-vertebrates; vertebrates, having more complex genetic systems, have the higher rates; in humans, for instance, around 60% genes undergo alternative splicing.
Once researchers understand how exactly the splicing process is regulated, they may be able to predict alternative splicing products from a given gene, which will be helpful as the outcomes of RNA alternative splicing vary and include turning a gene off and changing the function of a protein.