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RNA splicing

life science Maturity 11-13 Next article →

RNA splicing is a vital process in molecular biology. It transforms a newly made precursor messenger RNA (pre-mRNA) transcript into a mature messenger RNA (mRNA). This transformation is necessary for eukaryotic genes that contain non-coding regions. The process is a central part of gene expression, which is often called the central dogma of molecular biology.

Process of RNA splicing
Process of RNA splicing

Through splicing, the cell ensures that the genetic instructions are correctly formatted for protein production.

To understand the mechanism, we must look at the two main parts of the RNA transcript. These are called exons and introns. Exons are the coding regions that contain the actual instructions for proteins. Introns are non-coding regions located between the exons. During splicing, the cell removes all the introns and joins the exons back together. For most eukaryotic genes, this happens in the nucleus. It occurs either during or immediately after the process of transcription.

Most splicing is catalyzed by a large molecular machine called the spliceosome. The spliceosome is a complex made of proteins and small nuclear ribonucleoproteins, or snRNPs. The major spliceosome uses five specific snRNPs: U1, U2, U4, U5, and U6. It follows a very precise sequence of steps to function. First, it forms Complex E by binding to the intron's 5' splice site and branch point. It then progresses through several stages, including Complex A and the pre-catalytic Complex B.

RNA splicing reaction
RNA splicing reaction

In the final catalytic stage, known as Complex C, the intron is cut and forms a loop shape called a lariat. The exons are then joined together, and the lariat is released to be degraded.

Inside the intron, there are specific landmarks that the spliceosome must find. The 5' end of the intron is the donor site, which usually starts with a GU sequence. The 3' end is the acceptor site, which usually ends with an AG sequence. Between these lies a branch site containing an adenine nucleotide. There is also a polypyrimidine tract, which is a region high in cytosine and uracil, located upstream from the acceptor site. If a mutation occurs in these sequences, it can create a cryptic splice site. This might cause a section of an exon to be accidentally deleted from the final protein.

Nature provides several different pathways for splicing depending on the structure of the intron. Most splicing is "canonical," or the lariat pathway, which accounts for more than 99% of cases. However, a minor spliceosome exists to handle rare introns that do not follow the standard GU-AG rule. These minor introns use different snRNPs, such as U11, U12, U4atac, and U6atac. There is also trans-splicing, where exons from two different RNA transcripts are joined together.

Intron miguelferig
Intron miguelferig

Some organisms even use specialized methods like tRNA splicing or SOS splicing to protect their genes.

Some introns are unique because they do not need a spliceosome at all. These are called self-splicing introns, and they act as ribozymes. A ribozyme is an RNA molecule that can catalyze its own chemical reactions. There are three groups of these: Group I, Group II, and Group III. Group I and II introns perform splicing similar to the spliceosome by using two transesterification reactions. They both use magnesium ions in their catalytic core to help the reaction happen. Because they function without proteins, scientists think they may be very ancient and part of an early "RNA world."

Splicing also allows for incredible biological diversity through a process called alternative splicing. In this method, the cell can choose which exons to include or skip. This means a single gene can produce many different versions of a protein. It is estimated that 95% of transcripts from multiexon genes undergo alternative splicing. This flexibility is a major reason why complex life can exist. It allows a limited number of genes to create a vast array of specialized tools for the cell.

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File:Process of RNA splicing.png
Process of RNA splicing.png
File:Intron miguelferig.jpg
Intron miguelferig.jpg
File:RNA splicing reaction.svg
RNA splicing reaction.svg
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