An intron is a segment of a gene that does not contain instructions for building proteins or functional RNA molecules. These sequences are found within the gene and are removed during gene expression, undergoing a specific modification before the final genetic message is ready for cellular use.
Understanding Introns
Introns are non-coding sequences of DNA found within genes, typically in eukaryotic organisms like humans, animals, and plants. These sequences interrupt the coding segments of a gene, which are known as exons. Exons contain the genetic information that will be translated into proteins or will form functional RNA molecules. When a gene is transcribed from DNA into RNA, both exons and introns are included in this precursor RNA molecule, known as pre-messenger RNA (pre-mRNA).
The existence of introns was a surprising discovery in 1977, challenging the earlier view that genes were continuous stretches of coding information. For a period, introns were often referred to as “junk DNA” because their non-coding nature led to the misconception they served no purpose, as they are ultimately removed from the genetic message. However, modern understanding reveals a far more complex and functional role for these sequences within the genome.
The Splicing Process
The removal of introns from the pre-mRNA molecule is a cellular mechanism called RNA splicing. This process occurs in the cell’s nucleus, either during or immediately after gene transcription. Splicing is a necessary step for most eukaryotic genes to produce a mature messenger RNA (mRNA) molecule that can be translated into a protein.
The machinery responsible for splicing is a protein-and-RNA complex known as the spliceosome. It is composed of smaller units called small nuclear ribonucleoproteins (snRNPs). These snRNPs recognize specific nucleotide sequences at the boundaries between introns and exons, known as splice sites, such as “GU” at the start and “AG” at the end of an intron.
Once recognized, the spliceosome cuts the pre-mRNA at these specific sites, excising the intron. Following intron removal, the spliceosome ligates, or stitches, the remaining exon sequences together. This joining of exons creates a continuous, mature mRNA molecule that carries the coding instructions for a protein, which can then be transported to the cytoplasm for translation.
Beyond “Junk DNA”
The earlier notion of introns as “junk DNA” has been revised, as research has uncovered many functions for these non-coding regions. A primary role of introns is their involvement in alternative splicing. This process allows a single gene to produce multiple different mRNA molecules, and consequently, multiple distinct protein variants, by including or excluding certain exons. For example, the human genome has approximately 20,000 protein-coding genes, but alternative splicing can lead to a much larger number of unique protein forms, expanding the functional diversity of proteins an organism can produce.
Introns also play a role in gene regulation, influencing how and when genes are expressed. They can contain various regulatory elements, such as enhancers and silencers, which are DNA sequences that bind to specific proteins to either boost or dampen gene activity. These elements within introns can affect the efficiency of transcription or the stability of the mRNA molecule. Some introns can even encode functional RNA molecules themselves, which are not translated into proteins but instead perform regulatory roles within the cell.
Introns also contribute to evolutionary processes, such as facilitating gene recombination. Their presence allows for the shuffling of exon segments, creating new combinations of coding sequences that may lead to novel protein functions over evolutionary time. This “exon shuffling” mechanism can accelerate the evolution of new genes without disrupting existing functional domains. Introns also provide a level of protection against mutations, as changes within an intron are less likely to disrupt protein coding compared to mutations in exons.
Introns and Disease
Despite their roles, errors involving introns and the splicing process can have consequences for human health. Mutations within intronic sequences, particularly at splice sites, can disrupt the removal of introns from pre-mRNA. These “splicing mutations” can lead to improper exon recognition, causing exons to be skipped or introns to be retained in the mature mRNA.
Such errors can result in the production of non-functional or abnormally structured proteins, or they can alter the overall amount of protein produced. For example, mutations in genes like BRCA1 or BRCA2, associated with an increased risk of breast and ovarian cancer, can affect splicing. Improper splicing is also implicated in various neurodegenerative diseases and other genetic disorders.