How Does Alternative RNA Splicing Affect Gene Expression

Gene expression refers to a process by which the genetic information of a gene is transferred to an amino acid sequence of a functional protein. The flow of genetic information from DNA to RNA occurs through transcription. The RNA is decoded to produce the amino acid sequence of a polypeptide by translation. In eukaryotes, the regulation of gene expression occurs through many steps between transcription and translation. Generally, eukaryotic genes are more complex than prokaryotic genes as they contain extra sequences, interrupting the coding sequence. The coding sequence can be found in exons while the interrupting sequences are the introns. These introns are removed during post-transcriptional modifications in a process known as RNA splicing. Alternative RNA splicing is involved in the production of different proteins via the recombination of exons in different patterns. 

Key Areas Covered

1. What is RNA Splicing
     – Definition, Mechanism of RNA Splicing
2. How Does Alternative RNA Splicing Affect Gene Expression
     – The Production of Different Functional Proteins in Alternative Splicing

Key Terms: Exons, Introns, Multiple Proteins, RNA Splicing, Post-Transcriptional Modifications, Spliceosome A

What is RNA Splicing

RNA splicing refers to the initial stage of post-transcriptional modifications in eukaryotic gene expression. The initial transcript produced by transcription of a gene is known as pre-mRNA. It consists of both exons and introns. The introns are removed from pre-mRNA by the splicing of exons prior to translation. The splicing of exons is catalyzed by a molecular complex known as spliceosome. The spliceosome includes 5’ to 3’ splice site and a branch site. These subunits interact with the small nuclear ribonuclearproteins (snRNP) in the splicosome to produce the spliceosome A complex, which is responsible for the determination of the cleavage sites of the pre-mRNA. Once introns are cleaved out from the pre-mRNA, the exons are joined together via phosphodiester bonds. The spliceosome A complex is shown in figure 1.

Figure 1: Spliceosome A Complex

Different mRNA copies can be produced from the same pre-mRNA by alternating the combination pattern of exons during RNA splicing.

How Does Alternative RNA Splicing Affect Gene Expression

Alternative splicing is a process of RNA splicing that allows the production of multiple proteins from a single pre-mRNA molecule. It is achieved by the recombination of exons in different patterns. The production of multiple proteins during alternative splicing is shown in figure 2.

Figure 2: Production of Multiple Proteins in Alternative Splicing

The determination of the exons to be included in a protein is determined by the regulatory proteins. These regulatory proteins are the trans-acting proteins such as splicing activators and splicing repressors. The splicing activators promote some splicing sites to be included in the mRNA while splicing repressors reduce the inclusion of a particular splicing site. Heterogeneous nuclear ribonucleoprotein (hnRNP) and polypyrimidine tract binding protein (PTB) some of the splicing repressors. 

Conclusion

RNA splicing is the initial step of post-transcriptional modifications, which allows the removal of introns from pre-mRNA. Spliceosome A complex is responsible for the cleavage of intron and recombining of exons. During RNA splicing, the patterns of recombining the exons can be altered in a process known as alternative splicing. The alternative splicing of exons allows the production of different amino acid sequences of different functional proteins.

Reference:

1. “Eukaryotic Gene Regulation.” Lumen; Boundless Biology, Available here.

Image Courtesy:

1. “A complex” By Agathman – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “DNA alternative splicing” By National Human Genome Research Institute –  (Public Domain) via Commons Wikimedia