Group II intron
Group II introns are a class of RNA molecules found in the genes of certain organisms, including bacteria, archaea, and eukaryotic organelles such as mitochondria and chloroplasts. They are self-splicing introns that are capable of removing themselves from RNA transcripts without the need for additional proteins, although sometimes proteins can enhance their splicing efficiency. Group II introns are considered to be evolutionary ancestors of the spliceosome, the complex responsible for splicing pre-mRNA in eukaryotic cells.
Structure and Mechanism
Group II introns have a complex three-dimensional structure that allows them to catalyze their own excision from an RNA transcript. Their structure is typically divided into six domains (I-VI), with domain V being the catalytic center responsible for splicing. The splicing mechanism of group II introns involves two transesterification reactions. The first reaction is initiated by a bulged adenosine in domain VI attacking the 5' splice site, forming a lariat structure. The second reaction involves the 3' OH of the exon attacking the 3' splice site, resulting in the ligation of the exons and the release of the intron lariat.
Evolutionary Significance
Group II introns are thought to be the evolutionary precursors to the spliceosomal introns found in higher eukaryotes. This hypothesis is supported by similarities in the splicing mechanisms and structural features of group II introns and the spliceosome. Additionally, the presence of group II introns in the genomes of bacteria and organellar DNA suggests a role in the evolution of genes and genetic material transfer mechanisms across different domains of life.
Biotechnological Applications
Due to their self-splicing capability and site-specific integration into DNA, group II introns have been explored as tools for genetic engineering and gene therapy. They can be engineered to target specific DNA sequences, making them useful for gene disruption, modification, and repair in various organisms.
Classification
Group II introns are classified into two subgroups, IIA and IIB, based on structural and functional differences. This classification is further refined by sequence and structural analyses, which have identified several subfamilies within these groups.
Challenges and Future Directions
While group II introns hold promise for biotechnological applications, several challenges remain. These include improving their efficiency and specificity in targeting DNA sequences, understanding their potential impacts on host genomes, and developing safe and effective delivery methods for therapeutic applications.
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Contributors: Prab R. Tumpati, MD