DNA contains the instructions for building and operating our bodies. These instructions are organized into segments called genes, which serve as blueprints for producing proteins and other functional molecules. The way this information is arranged and processed is complex, involving specific components.
Exons: The Building Blocks of Proteins
Exons are the segments within a gene that contain the genetic information directly translated into proteins. Think of exons as meaningful sentences in an instruction manual. After a gene’s DNA is copied into an RNA molecule, these exons are the parts that remain to form the final messenger RNA (mRNA), which then guides protein synthesis. Exons can include regions that code for amino acids, as well as untranslated sequences at their ends that help regulate protein production.
Introns: The Intervening Sequences
Introns, in contrast to exons, are non-coding regions found within a gene. These segments are transcribed into RNA along with exons, but they do not carry instructions for building proteins. Instead, introns are located between the exons and are removed from the RNA molecule before it is used for protein synthesis. Introns can vary significantly in length and number, with some genes containing many introns, while others have none.
The Splicing Mechanism
The process of removing introns and joining exons together is called RNA splicing. This occurs after a gene is transcribed into a precursor messenger RNA (pre-mRNA) molecule, usually within the cell’s nucleus. A molecular machinery known as the spliceosome carries out this operation. The spliceosome, composed of small nuclear ribonucleoproteins (snRNPs) and other proteins, recognizes specific sequences at the beginning and end of each intron, called splice sites, along with a branch point within the intron.
The splicing process involves two main biochemical steps, known as transesterification reactions. First, the spliceosome cuts the pre-mRNA at the 5′ end of the intron, and this end then loops back to connect to the branch point, forming a lasso-like structure called a lariat. Next, the spliceosome cuts the intron at its 3′ end, simultaneously joining the two adjacent exons. This process ensures that only the protein-coding exons are connected in the correct order, producing a mature mRNA molecule ready for protein production.
The Evolutionary Role of Introns
While introns do not directly code for proteins, they play a role in gene expression regulation and evolution. Introns can contain regulatory elements that influence how and when genes are expressed. They can enhance the expression of a gene or affect the stability and transport of the mRNA molecule.
A key function of introns is their involvement in alternative splicing, a mechanism that allows a single gene to produce multiple different protein versions. During alternative splicing, different combinations of exons from the same gene can be included or excluded in the final mRNA molecule. This process increases the diversity of proteins an organism can create from a limited number of genes, contributing to cellular differentiation and complexity. For instance, the human genome is estimated to generate at least two alternative mRNA forms from almost all genes, with an average of seven mRNA isoforms per gene.
When Splicing Goes Wrong
Errors or mutations affecting the splicing process can impact cellular function and human health. If splicing is improper, it can lead to the production of non-functional proteins or proteins with altered functions. Such errors might occur if a mutation changes a splice site sequence, preventing the spliceosome from recognizing it correctly.
These splicing defects are linked to a range of genetic diseases. For example, conditions like certain cancers, neurological disorders, and muscular dystrophies can arise from mis-splicing events. One well-known instance is beta-thalassemia, a blood disorder where a mutation causes faulty splicing of a gene involved in hemoglobin production, leading to non-functional hemoglobin. Approximately 10% of mutations associated with human diseases are thought to affect splice sites, underscoring the importance of accurate splicing for health.