premRNAsplicing

PremRNA splicing, also known as eukaryotic mRNA splicing, is a fundamental process in gene expression where introns—non-coding sequences—are excised from precursor messenger RNA (pre-mRNA) and exons—coding sequences—are joined together to produce a mature, functional mRNA. This process occurs primarily in the nucleus of eukaryotic cells and is essential for generating diverse protein isoforms from a single gene.

The splicing machinery consists of small nuclear ribonucleoproteins (snRNPs), collectively called the spliceosome, along with other proteins and non-coding RNAs. The spliceosome recognizes specific nucleotide sequences at the boundaries of introns: the 5' splice site (GU dinucleotide), the 3' splice site (AG dinucleotide), and a branch point adenine residue within the intron. These sites are conserved across many eukaryotic genes, though exceptions exist.

Splicing begins with the formation of a lariat structure, where the branch point adenine attacks the 5' splice site, creating an exon-intron junction. The intron is then cleaved, and the 3' end of the upstream exon attacks the 3' splice site, ligating exons together while releasing the intron as a lariat. Alternative splicing, a regulated process, allows a single pre-mRNA to be spliced in multiple ways, increasing proteomic diversity without expanding the genome.

Defects in splicing can lead to genetic disorders, such as those caused by mutations in splice sites or splicing factors. Diseases like β-thalassemia and spinal muscular atrophy arise from improper splicing, highlighting its clinical significance. Additionally, splicing is tightly controlled by regulatory elements, including exonic and intronic enhancers/silencers, which influence splice site selection in response to developmental or environmental cues.