Cells detect and silence invading transposons through abnormal RNA signals

While the work was conducted in yeast, similar defensive mechanisms are also likely to exist in higher organisms, particularly in germline cells (sperm and eggs), which are particularly vulnerable to transposon-induced disruption.

Mario Halic, PhD, St. Jude Department of Structural BiologyEvery organism tries to defend itself from transposon invasion; they can proliferate uncontrollably and occupy large parts of the genome, slowing growth and negatively affecting gene expression. Defensive systems like this are typically restricted to germline cells, where strong defense is essential. Otherwise, a transposon could propagate dramatically within just a few generations."

Transposon silencing works for all invasive DNA

For their study, the researchers introduced an invasive transposon into cells and monitored as it jumped into different locations within the yeast genome. They then sequenced those locations and measured DNA copy number and RNA levels to see how efficiently they were silenced. Yeast strains that initially generated more RNA from the invading DNA were found to be more effective at detecting and silencing it, but the system that governs this is high-risk, high-reward, as the researchers note.

"Heterochromatin has a habit of spreading, silencing not only the transposon but also nearby genes," Halic said. "Yeast cells that silence transposons this way initially grow slower, which is a disadvantage, but it becomes beneficial if transposons proliferate. This may explain why human adult cells use safer, more targeted systems instead of this broad silencing mechanism."

"What excited us most was discovering that the cells don't just silence transposons, they can silence any invasive DNA, as long as it produces enough RNA," said co-first author Yinxia Yan, PhD, Department of Structural Biology. "This showed us that the cellular defense system is even smarter than we thought."

Source:

St. Jude Children's Research Hospital

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