Genome complexity: new editing systems found (Introduction)

by David Turell , Thursday, September 30, 2021, 22:19 (1151 days ago) @ David Turell

Transposons controlling RNA's found in early new research:

https://www.science.org/doi/full/10.1126/science.abj6856?af=R

"Abstract
IscB proteins are putative nucleases encoded in a distinct family of IS200/IS605 transposons and are likely ancestors of the RNA-guided endonuclease Cas9, but the functions of IscB and its interactions with any RNA remain uncharacterized. Using evolutionary analysis, RNA sequencing, and biochemical experiments, we reconstructed the evolution of CRISPR-Cas9 systems from IS200/IS605 transposons. We found that IscB uses a single noncoding RNA for RNA-guided cleavage of double-stranded DNA and can be harnessed for genome editing in human cells. We also demonstrate the RNA-guided nuclease activity of TnpB, another IS200/IS605 transposon-encoded protein and the likely ancestor of Cas12 endonucleases. This work reveals a widespread class of transposon-encoded RNA-guided nucleases, which we name OMEGA (obligate mobile element–guided activity), with strong potential for developing as biotechnologies.

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"Discussion
Naturally programmable biological systems offer an efficient solution for diverse organisms to achieve scalable complexity via modularity of their components. RNA-guided defense and regulatory systems, which are widespread in prokaryotes and eukaryotes, are a prominent case in point, and have served as the basis of numerous biotechnology applications thanks to the ease with which they can be engineered and reprogrammed.

Here, through the exploration of Cas9 evolution, we discovered the programmable RNA-guided mechanism of three highly abundant but previously uncharacterized transposon-encoded nucleases: IscB, IsrB, and TnpB, which we collectively refer to as OMEGA (obligate mobile element–guided activity) because the mobile element localization and movement likely determines the identity of their guides. Although the biological functions of OMEGA systems remain unknown, several hypotheses are compatible with the available evidence, including roles in facilitating TnpA-catalyzed, RNA-guided transposition, or acting as a toxin, with the transposon acting as the antitoxin, securing maintenance of IS200/IS605 insertions."

Comment: This highly complex mechanism is not fully understood as yet. But it is obviously irreducibly complex and was designed at the initiation of DNA coding. Chance cannot produce this.