Plants such as Arabidopsis depend on a molecule named DDM1 to accurately transmit chromosome copies to subsequent generations. Despite DDM1’s significance, Arabidopsis does not appear to suffer when it is absent. After three decades, botanists have uncovered the explanation: Arabidopsis has a contingency plan called RNAi.
Gardening can be quite challenging, but think about it from the perspective of the plants. Each plant depends on precisely regulated genetic mechanisms to ensure that chromosome copies are accurately inherited across generations. These mechanisms often involve a multitude of components. Even the smallest disruption can lead to significant consequences. Thus, for plants like Arabidopsis thaliana, having a backup system is crucial.
“For a cell to divide correctly, chromosomes need to be separated accurately,” says Rob Martienssen, a Professor at Cold Spring Harbor Laboratory (CSHL) and HHMI Investigator. “The centromere on each chromosome plays a key role in this separation process, aided by the molecule DDM1 in plants.”
Martienssen and a research team, which included Tetsuji Kakutani, discovered DDM1 in 1993. Recently, Martienssen and Kakutani collaborated to explore a question that has lingered for 30 years. While humans experience severe genetic conditions, such as ICF syndrome, when they lose DDM1, why does Arabidopsis remain unaffected?
“We were curious about this discrepancy. About a decade later, we learned that small RNAs govern centromere function in yeast, a mechanism known as RNAi. Plants possess both DDM1 and RNAi. So we thought, ‘Let’s see what happens when we isolate these two in Arabidopsis.’ We proceeded with that, and unsurprisingly, the plants ended up looking quite unhealthy,” Martienssen explains.
Upon closer inspection, the researchers discovered that a particular transposon on chromosome 5 was causing the issues. Transposons can relocate within the genome, turning genes on and off. For Arabidopsis, these transposons either activate DDM1 or RNAi to facilitate centromere division. However, the absence of DDM1 and RNAi disrupts this process.
“We noticed very few copies of the problematic transposon scattered throughout the genome,” says Martienssen. “Yet, the centromere of chromosome 5 was overrun with them. We immediately thought, ‘This could be the root of the problem.’ So we began to investigate how we could restore proper function.”
Martienssen, along with the study’s lead author, Atsushi Shimada, created short hairpin RNAs to target the transposons.
“These small RNAs compensate for the absence of DDM1. They identified every instance of the transposon within the centromere and, astonishingly, restored its functionality. As a result, the plants became fertile again, and their appearance improved significantly,” Martienssen remarks.
Importantly, this research has implications beyond the plant world. In humans, irregular centromere division has been associated with disorders like ICF and early stages of cancer. Martienssen hopes that the findings from his team’s study may eventually lead to enhanced treatments for these and other health issues.
