The lariat structure refers to a distinctive looped shape formed by a molecule of RNA. This unique conformation is characterized by an unusual bond that creates a closed circle with a short tail. While once considered merely a transient byproduct, recent research suggests some lariats can be more stable and might even have their own biological functions within the cell. The presence of this specific looped architecture is a fundamental aspect of how genetic information is processed within living organisms.
The Lariat Structure in RNA Splicing
The lariat structure plays a significant role in RNA splicing, a cellular process that refines genetic messages. Genes are stored in DNA and first copied into pre-messenger RNA (pre-mRNA). In humans and many other organisms, pre-mRNA molecules contain exons, which carry protein-building instructions, interspersed with non-coding introns.
Before pre-mRNA can be used to create a protein, introns must be precisely removed, and exons stitched together. This process, RNA splicing, ensures that only the relevant information is conveyed to the cell’s protein-building machinery. The lariat structure is a temporary but necessary intermediate that forms when an intron is excised during this splicing event. Its formation is a central step in converting raw genetic information into functional proteins, as any mistake in intron removal can lead to faulty protein products.
How the Lariat Structure Forms
The formation of the lariat structure is a two-step biochemical process driven by the spliceosome. This complex is assembled from small nuclear RNAs (snRNAs) and numerous proteins. The spliceosome recognizes specific sequences at the boundaries of introns and exons.
The first step involves a nucleophilic attack where the 2′-hydroxyl (2′-OH) group of an adenosine nucleotide at the intron’s branch point attacks the phosphate at the 5′ splice site of the intron. This reaction cleaves the pre-mRNA at the 5′ end of the intron and creates a 2′-5′ phosphodiester bond, which is different from the usual 3′-5′ bonds that link nucleotides in a linear RNA chain. This bond forms the closed loop of the lariat structure, with the 5′ end of the intron now covalently linked to the branch point adenosine. After the lariat is formed, the spliceosome undergoes a conformational change, positioning the newly freed 5′ exon for the next step.
Consequences of Lariat Formation and Splicing Errors
Accurate lariat formation and successful splicing are important for proper gene expression and the synthesis of functional proteins. After the second transesterification reaction, which joins the exons and releases the intron, the lariat structure is debranched and degraded by cellular machinery. The RNA debranching enzyme DBR1 primarily carries out this degradation, which specifically cleaves the unusual 2′-5′ phosphodiester bond.
If lariat formation or splicing goes awry, the consequences can be serious for cellular health. Splicing errors can lead to non-functional proteins or altered gene products, contributing to various genetic diseases. For instance, mutations affecting splice sites or branch points can result in improper intron removal, leading to the inclusion of intronic sequences or the exclusion of exons in the mature mRNA. Such errors can disrupt the protein-coding sequence, leading to truncated or otherwise non-functional proteins. Many hereditary diseases, including certain forms of cancer and neurological disorders, have been linked to these splicing defects.