What is the Difference Between RNA Splicing and Alternative Splicing

The main difference between RNA splicing and alternative splicing is that the RNA splicing is the process of splicing the exons of the primary transcript of mRNA whereas the alternative splicing is the process of producing differential combinations of exons of the same gene. Furthermore, RNA splicing is responsible for the production of a mRNA molecule that can be translated into a protein while alternative splicing is responsible for the production of a range of proteins from the same primary transcript.

RNA splicing and alternative splicing are two types of post-transcriptional modifications that follow the transcription of eukaryotic genes. Both are important for the production of a functional protein.

Key Areas Covered

1. What is RNA Splicing
     – Definition, Process, Importance
2. What is Alternative Splicing
     – Definition, Process, Importance
3. What are the Similarities Between RNA Splicing and Alternative Splicing
     – Outline of Common Features
4. What is the Difference Between RNA Splicing and Alternative Splicing
     – Comparison of Key Differences

Key Terms

Alternative Splicing, Exons, Introns, Post-Transcriptional Modifications, RNA Splicing

What is RNA Splicing

RNA splicing is the biological process that removes the introns from the primary RNA transcript while ligating the exons together in eukaryotes. In humans, the average length of a gene is 30,000 base pairs, but the length of a mature mRNA molecule is less than 20,000 base pairs. RNA splicing is responsible for this reduction of the average length of the mRNA molecule. The main function of the RNA splicing process is the production of a mature mRNA molecule from the primary RNA transcript, which can be translated into a functional protein.

Figure 1: RNA Splicing

Generally, each intron starts with a GU and ends with an AG in the 5’ to 3’ direction. The former is the splicing donor site while the latter is the splicing acceptor site. A third site called the branch site occurs 20 – 50 bases upstream to the acceptor site with a consensus sequence of the branch site “CU(A/G)A(C/U)”, where A is conserved in all genes. These three sites are collectively known as the splicing signals. In addition, the exon sequence of the donor site is (A/C)AG in most of the cases, and the exon sequence at the acceptor site is G.

Figure 2: Two-Step Mechanism of RNA Splicing

Five snRNA molecules and their associated proteins form a ribonuclear protein called the splicosome, which is a large (60S) complex. The splicosome is responsible for the removal of the introns from the primary RNA transcript in a two-step process. Meanwhile, Constitutive splicing is the general RNA splicing mechanism.

What is Alternative Splicing

Alternative splicing is the biological process responsible for the production of variant mRNA molecules from a particular primary RNA transcript of a particular gene. That means; the expression of a single gene can result in multiple proteins with the help of alternative splicing. Therefore, these mature mRNA molecules may lack some of the exons in the primary RNA transcript. As the amino acid sequence of these proteins differs from each other, they exert different biological functions inside the cell. Though the human genome consists of 25,000-35,000 protein-coding genes, over 90,000 of proteins are synthesized as a result of alternative splicing. Moreover, multiple proteins synthesized from a particular RNA transcript are called protein isoforms.

Figure 3: Alternative Splicing Overveiw

There are five basic modes of alternative splicing. They are the exon skipping or the cassette-type alternative exon, mutually exclusive exons, alternative 3’ splice site, alternative 5’ splice site, and intron retention. The most prevalent pattern of alternative splicing in vertebrates and invertebrates is exon skipping. In lower metazoans, it is the intron retention.

Figure 4: Mechanisms of Alternative Splicing

Similarities Between RNA Splicing and Alternative Splicing

• RNA splicing and alternative splicing are two types of post-transcriptional modifications which occur during eukaryotic gene expression.
• However, the effector molecule for both processes is the primary RNA transcript.
• Also, both involve in the splicing of exons by removing introns.
• Furthermore, both are responsible for the production of a mRNA molecule, which can translate into a functional protein.
• In addition, both processes occur inside the nucleus.

Difference Between RNA Splicing and Alternative Splicing

Definition

RNA splicing refers to a modification of the nascent pre-messenger RNA (pre-mRNA) transcript in which introns are removed and exons are joined prior to translation. Whereas, alternative splicing refers to a process that enables a messenger RNA (mRNA) to direct synthesis of different protein variants (isoforms) that may have different cellular functions or properties. These defintions explain the fundamental difference between RNA splicing and alternative splicing.

Function

RNA splicing splices the exons of the primary RNA transcript while alternative splicing splices the exons in the primary RNA transcript, forming differential combinations of exons. Hence, this is the functional difference between RNA splicing and alternative splicing. 

Exons

Moreover, the mature mRNA produced by RNA splicing contains all the exons in the primary transcript while the mature mRNAs produced by alternative splicing do not contain every exon of the primary RNA transcript.

Results in

Another difference between RNA splicing and alternative splicing is the outcome of the splicing. RNA splicing results in mRNA molecule, which can translate into a functional protein while alternative splicing results in different mRNA variants, which can translate into different protein isomers.

Importance

The difference between RNA splicing and alternative splicing based on their importance is that the RNA splicing brings the protein coding region together by removing the non-coding regions from the primary transcript while alternative splicing increases the informational diversity and the proteomic diversity of the cell.

Conclusion

RNA splicing is the process of ligating the exons of the eukaryotic pre mRNA by removing the introns. On the other hand, alternative splicing is the production of multiple mRNAs from a single pre mRNA by the differential combination of exons. The main function of RNA splicing is to produce a mature mRNA, which can be translated into a functional protein. Conversely, alternative splicing produces protein isomers with differential functioning. Therefore, the main difference between RNA splicing and alternative splicing is their mechanism and importance.

Reference:

1. E, Zhiguo et al. “Splicing and alternative splicing in rice and humans” BMB reports vol. 46,9 (2013): 439-47. Available Here
2. “RNA Splicing.” MoBio, Web Books Publishing, Available Here
3. Wang, Yan et al. “Mechanism of alternative splicing and its regulation” Biomedical reports vol. 3,2 (2014): 152-158. Available Here

Image Courtesy:

1. “RNA splicing diagram en” By LadyofHats – made myself based basically in the information found in wikipedia plus :[1]and[2]. (Public Domain) via Commons Wikimedia  
2. “RNA splicing reaction” By BCSteve – Own work (CC BY-SA 3.0) via Commons Wikimedia  
3. “DNA alternative splicing” By National Human Genome Research Institute – http://www.genome.gov/Images/EdKit/bio2j_large.gif (Public Domain) via Commons Wikimedia  
4. “RNA Splicing” By OpenStax CNX (CC BY 3.0) via OpenStax Collage