RNA splicing was first discovered in 1970s in viruses and subsequently in eukaryotes.  Not long after, scientists discovered alternative patterns of pre-mRNA splicing that produced different mature mRNAs containing various combinations of exons from a single precursor mRNA. The first example of alternative splicing of a cellular gene in eukaryotes was identified in the IgM gene, a member of the immunoglobulin superfamily. Alternative splicing (AS) therefore is a process by which exons or portions of exons or noncoding regions within a pre-mRNA transcript are differentially joined or skipped, resulting in multiple protein isoforms being encoded by a single gene. This mechanism increases the informational diversity and functional capacity of a gene during post-transcriptional processing and provides an opportunity for gene regulation.

The mechanism of alternative splicing

During alternative splicing, cis-acting regulatory elements in the mRNA sequence determine which exons are retained and which exons are spliced out. These cis-acting regulatory elements alter splicing by binding different trans-acting protein factors, such as SR (Serine-Arginine rich) proteins that function as splicing facilitators, and heterogeneous nuclear ribonucleoproteins (hnRNPs) that suppress splicing. Inhibition of silencing could be achieved sterically, when binding of splicing inhibitors to splicing silencers located in close proximity to splicing enhancers blocks the binding of snRNPs and other activator proteins or prevents the spliceosome assembly. The final decision to include or splice an alternative exon is thus determined by combinatorial effects, cellular abundance, and competitive binding between SR activators and hnRNP inhibitors. The outcome of alternative splicing depends on the stoichiometry and interactions of splicing activators and inhibitors as well as the steric conformation and accessibility of the splicing sites.

Regards,

Angelina Matthew,

Managing Editor,

Journal of Genetics and Genomes

Email Id: genetics@scholarlypub.com