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Jumping Genes: From Discovery to Potential Cure
Context: On June 26, researchers from UC Berkeley and the Arc Institute revealed a new RNA-guided gene editing system in Nature.
- It utilizes a gene from the IS110 bacterial transposon family, enabling cells to produce an RNA molecule with dual loops for precise genome editing.
RNA-guided transposons
- Researchers discovered RNA capable of binding to two DNA pieces simultaneously, forming a bridge for precise DNA editing in a new study.
- The two loops of the RNA can independently bind to two separate pieces of DNA.
- One of the loops identifies the target site in the genome that needs to be altered while the other loop specifies the DNA to be inserted.
- Each loop is independently programmable, which means researchers can mix and match any target and donor DNA sequences of interest.
- In Escherichia coli bacteria, the bridge RNA demonstrated over 60% insertion efficiency and 94% specificity for targeting specific genomic locations.
 In a separate study from the University of Tokyo, researchers detailed how bridge RNA guides genome modification.
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From Static to Dynamic Genes: Understanding Discovery of Transposon
- In 1948, Barbara McClintock challenged the notion of genes as stable and orderly arranged on chromosomes.
- Studying maize kernels, she discovered mobile elements known as transposons, or “jumping genes,” that could move around within the genome.
- McClintock’s findings earned her the Nobel Prize in Physiology or Medicine in 1983.
Sleeping Beauty Transposon
- In 1997, researchers studied fish genomes and reconstructed a dormant transposon called ‘sleeping beauty’ at the molecular level. This transposon had become inactive in vertebrates millions of years ago.
- They influence the effects of genes by turning ‘on’ or ‘off’ their expression using a variety of epigenetic mechanisms.
- More than 45% of the human genome comprises transposable elements, which contribute to genetic diversity but can also cause gene mutations and diseases. However, many transposons have accumulated mutations over time, rendering them inactive and unable to move within the genome.
- Researchers have endeavoured to revive inactive transposons from animal genomes for biomedical applications.
- To utilise them for genetic corrections to treat diseases or for advanced gene therapy techniques.
Significance of RNA Bridge
- This technology can add, remove, recombine, and reverse DNA sequences, overcoming the limitations of existing gene-editing tools such as CRISPR23.
- This technique enables researchers to insert desired genetic material into specific genomic locations, treating genetic diseases by replacing faulty genes.
- It holds promise for synthetic biology applications, facilitating the insertion or removal of entire gene sets in organisms.
- It may address challenges like chromosomal inversions or deletions that current editing tools struggle to manage effectively.
What is Transposon?
- Transposable elements (TEs), also known as “jumping genes,” are DNA sequences that move from one location on the genome to another.
- TEs are universal in both prokaryotic and eukaryotic organisms, existing in significant numbers.
- They constitute approximately 50% of the human genome and can reach up to 90% of the maize genome (San Miguel, 1996).
- Their mobility and abundance contribute to genetic diversity and evolutionary dynamics across species.