Question

Briefly explain how alternative patterns of RNA splicing give rise to multiple isoforms of proteins. Why is this an important form of post-transcriptional regulation?

Answer 1

During RNA splicing, exons are either retained in the mRNA or targeted for removal in different combinations to create a diverse array of mRNAs from a single pre-mRNA. This process is known as alternative RNA splicing

.Types of splicing alteration observed include exon skipping, intron retention and use of alternative splice donor or acceptor sites. These give rise to different protein isoforms in different tissues, developmental states, or disease conditions.

Constitutive splicing is the process of intron removal and exon ligation of the majority of the exons in the order in which they appear in a gene. Alternative splicing is a deviation from this preferred sequence where certain exons are skipped resulting in various forms of mature mRNA. Weaker splicing signals at alternative splice sites, shorter exon length or higher sequence conservation surrounding orthologous alternative exons influence the exons that are ultimately included in the mature mRNA This process is mediated by a dynamic and flexible macromolecular machine, the spliceosome, which works in a synergistic and antistatic manner Three possible mechanisms, exon shuffling, exonization of transposable elements and constitutively spliced exons, have been proposed for the origin of alternative splicing.

alternative patterns of RNA splicing is an important form of post-transcriptional regulation because-

Alternative splicing of eukaryotic transcripts is a mechanism that enables cells to generate vast protein diversity from a limited number of genes.

During RNA splicing, exons are either retained in the mRNA or targeted for removal in different combinations to create a diverse array of mRNAs from a single pre-mRNA.

alternative splicing has a role in almost every aspect of protein function, including binding between proteins and ligands, nucleic acids or membranes, localization and enzymatic properties.

Alternative splicing mediates diverse biological processes over the entire life span of organisms, from before birth to death . Conserved splicing to species-specific splice variants play a significant functional role in species differentiation and genome evolution , as well as in the development of functionally simple to complex tissues with diverse cell types, such as the brain, testis and the immune system. Alternative splicing even participates in RNA processing itself, from pre- to post-transcriptional events.