Jumping Genes (Transposons) and RNA Bridges

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Context (TH): Research found that RNA bridges can be used to resurrect inactive jumping genes.

Jumping Genes (Transposons)

In 1948, Barbara McClintock, a scientist working on the genetics of maize plants, challenged the prevailing notion that genes were stable and arranged in an orderly manner on chromosomes.
She found that some genes could move within the genome and reversibly alter gene expression. These genes were called mobile elements/transposons/jumping genes.
This earned her the Nobel Prize in Physiology or Medicine in 1983.
Transposons are found in various life forms, including bacteriophages, bacteria, plants, worms, fruit flies, mosquitoes, mice, and humans.
More than 45% of the human genome consists of transposable elements. They are essential for genetic diversity but can lead to mutations and diseases.
However, most transposons have themselves inherited mutations and become inactive (cannot move within the genome).

Transposons influence gene expression by turning it ‘on’ or ‘off’ using various epigenetic mechanisms.
They are called the tools of evolution for their ability to rearrange the genome and induce changes.
They may help treat chromosomal inversions or deletions, which current gene editing tools cannot do.
Researchers aim to revive inactive transposons for biomedical applications like genetic therapy.
The “sleeping beauty” transposon, which had become dormant in vertebrates millions of years ago, was reconstructed by studying fish genomes. This synthetic version was adapted for use in human cells.

Epigenetic mechanisms refer to modifications or changes in gene expression that do not involve alterations in the DNA sequence itself.

A new RNA-guided gene editing system has been developed, inspired by a gene from a family of bacterial transposons (IS110 family). This gene instructs cells to produce an RNA molecule with two loops.
Transposons contain recombinase enzymes that bind to other DNA.
So, this RNA with two loops can bind to two pieces of DNA, forming a bridge between them, unlike the usual binding to just one piece. This RNA bridge is used to edit the DNA.
Each loop has a specific job.
- Target binding loop: It recognises and binds to the target DNA that needs to be altered.
- Donor binding loop: It recognises and binds to a separate piece of DNA used for the editing.
Researchers can programme each loop independently, mixing and matching target and donor DNA sequences as needed.
The RNA bridge had more than 60% insertion efficiency (the ability to introduce a desired gene) and 94% specificity (the ability to target the intended location on the genome).
This technique is also called the bridge recombinase mechanism.

IS110 family bacterial transposons are found abundantly in E. Coli bacteria.

Feature	CRISPR-Cas9	RNA Bridge
Established	Yes	No (emerging)
Gene Editing method	Cuts and relies on cellular repair	Precise cutting and joining
Gene Editing capabilities	Limited (small insertions/deletions of DNA sequences)	More versatile (insertions, deletions, and inversions of DNA sequences)
Potential for Errors	Higher (leaves small bits of nucleotides added/deleted during the repair process)	Lower (makes a clean cut, making the edit specific and tidy)