RNA Splicing: Definition, Steps, Types and Examples

What Is RNA Splicing?

RNA splicing is one of the basic processes involved in gene expression within eukaryotes, in which pre-messenger RNA is converted into mature messenger RNA. In simple terms, it entails the removal of non-coding sequences (introns) and joining the coding sequencing (exons). The splicing process ensures that only those sequences of nucleotides representing coding information are retained in the mRNA for translation into a given protein.

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This forms the central mechanism of the flow of genetic information from DNA to RNA to proteins, what is called the central dogma of molecular biology. The integrity of the genetic code itself is intrinsic to the process of RNA splicing, for this will allow for the proper assembly of amino acids into functional proteins. The process involves the precise excision of introns and the ligation of exons.

Types Of RNA Splicing

The different types of RNA splicing are:

Constitutive Splicing

Constitutive splicing is the earliest or most primitive form, wherein introns are removed uniformly and exons are joined back continuously. This type of splicing occurs in all cells and ensures that the genetic code is expressed correctly in the mRNA.

Alternative Splicing

Alternative splicing allows the generation of multiple protein variants from a single gene. It includes specific exons or excludes them for the formulation of different mRNA transcripts. Some major types of alternative splicing include:

Exon Skipping: The selective skipping of some exons is called exon skipping, resulting in alternative mRNA isoforms.

Intron Retention: During this process, some introns may be retained in the final mRNA and finally alter the function of the protein.

Mutually Exclusive Exons: Only one of the exons in a series is included in the mRNA.

Alternate 5' Splice Site: Multiple splice sites are available at the 5' end of an exon.

Alternate 3' Splice Site: Multiple splice sites are available at the 3' end of an exon.

Alternative splicing provides various means of increasing protein diversity so that one gene might offer its contribution towards several physiological processes and cellular functions.

RNA Splicing Process

The process of RNA splicing is a complicated, yet well-orchestrated read series of events in its molecular components. Key to this is the spliceosome, a huge RNA-protein complex including small nuclear RNAs and associated proteins. Small nuclear RNAs and associated proteins interact in concert within the spliceosome to effect the precise removal of introns and joining of exons in a series of steps:

Recognition Of Splice Sites:

The spliceosome recognises specific sequences at the boundaries between an intron and an exon.

Lariat Formation And Exon Ligation:

The intron loops into a lariat structure and then gets excised, while exons get ligated.

Release Of The Intron Lariat:

Release of the intron lariat and its degradation efficiency ensures that only the mature mRNA will be translated into protein.

Regulation Of RNA Splicing

RNA splicing is regulated by both cis-acting elements and transacting factors.

Cis-Acting Element

These are the splicing enhancers and silencers, either within the exons, known as the exonic splicing enhancers/silencers, or in the introns, called intronic splicing enhancers/ silencers. The effectiveness of this element regarding splice site selection is based on the splicing factors with which they bind.

Trans Acting Factors

These extend from factors of splicing and regulatory proteins that interact with spliceosome/RNA to regulate splicing events to the cellular environment itself and its involved cellular signalling pathways capable of modulating splicing. This thus enables the cell to adapt to a wide spectrum of physiological conditions and stressors.

RNA Splicing Errors And Diseases

It forms the basis for several genetic and acquired human diseases, as RNA splicing errors can be detrimental.

Mutations at splice sites or regulatory elements perturb normal splicing patterns and lead to aberrant mRNA and, consequently, dysfunctional protein.

For instance:

Spinal Muscular Atrophy: Caused by mutations in the SMN1 gene that affect the splicing of the SMN2 pre-mRNA.

Cystic Fibrosis: Splicing mistakes in the CFTR gene lead to aberrant splicing and reduce the chloride ion transport.

Treatment Strategies

Novel promising therapies targeting splicing mistakes. Gene therapy provides functional copies of the defective genes, whilst splice-switching oligonucleotides alter the splicing patterns and can be exploited as a therapy for splicing-related diseases.

RNA Splicing: A Critical Process

RNA splicing is carried out to generate the huge diversity of proteins required for innumerable functions within a living organism. This process confers on a cell the capacity to express different isoforms of proteins from one gene, therefore increasing functional genome diversity. Moreover, splicing regulation allows tissue-specific expression and adaptation to environmental changes; hence, it is crucial for development, cell differentiation, and cellular stress response.

Conclusion

RNA splicing is a universal, complex process, and its proper execution is required for appropriate gene expression and protein synthesis. Constitutive and alternative splicing mechanisms allow cells to generate an extremely diverse proteome from a relatively small number of genes. Indeed, the regulation of RNA splicing assures the right interpretations of the genetic information; splicing errors thus lead to serious diseases. Knowing the subtleties of RNA splicing opens up new avenues for therapeutic interventions and puts sense into the complexity of gene regulation.