Photograph of two Arabidopsis plants that either are from a genotype deficient in DNA methylation and small interfering RNAs from transposable elements (right) or has been rescued with the introduction of short hairpin RNAs. Whereas the plant on the left has four white petals like a normal plant, the plant on the right lacks these petals.
Article

Small RNAs Save Plant Centromeres

Transposons embedded into the chromosome serve as a backup to keep division moving smoothly.

Shelby Bradford, PhD
Shelby Bradford, PhD
| 2 min read
Image creditAtsushi Shimada

Centromeres are important elements of chromosomes that are responsible for the proper separation of chromosomes during cell division. This function is closely related to appropriate methylation patterns that give the DNA its structure to bind the necessary proteins.

Top: Photograph of DNA methylation and short interfering RNA mutant (right) plants or those that have been rescued with short RNA hairpins. Bottom: Fluorescent microscopy image showing centromeres (blue) that either segregate appropriately (left) or improperly (right).

Rob Martienssen’s group showed that loss of DNA methylation and production of short interfering RNAs (top, right) leads to chromosomal segregation defects (bottom, right). These are rescued by the introduction of short RNA hairpins (left, top and bottom).

Atsushi Shimada/License CC-BY 4.0, Shimada et al, 2024, Nature Plants

Plants like Arabidoposis thaliana use a protein called decrease in DNA methylation 1 (DDM1) to methylate DNA to compact it, while human cells use a homologous protein. Loss of this protein in humans leads to a genetic syndrome, but A. thaliana plants that lacked DDM1 due to gene mutation continued to segregate chromosomes with no apparent impact on their phenotype.1 However, researchers previously found that these mutants activated a specific family of transposable elements (TEs) in their genome which produced short interfering RNAs that are involved in the RNA interference (RNAi) process that silence gene expression.2

“We wondered whether this RNAi might be somehow making up the loss of centromere function,” said Rob Martienssen, a plant geneticist at Cold Spring Harbor Laboratory. In a study published in Nature Plants, Martienssen and his team showed that one family of TEs enriched in the centromere of chromosome 5 in A. thaliana produced short hairpin RNAs that were integral to the proper structure and function of that centromere.3

In mutants that lacked DDM1 and RNAi machinery, the researchers found that chromosome 5 failed to segregate properly, causing infertility and other defects. They mapped the DNA region responsible for these effects to the centromere of chromosome 5 and determined that this region was enriched in their previously-identified TE family using long-read sequencing.

In the absence of DDM1 and RNAi, this TE doesn’t produce small RNAs, so the centromere is not methylated. These mutants also had few epigenetic tags on their histones, which contribute to the structure of the centromere.

When researchers supplied short RNA hairpins derived from this TE to the DDM1 and RNAi mutants, the hairpins promoted the proper epigenetic markers on the centromeric histones and reversed the chromosomal segregation defect.

Gernot Presting, a plant genomicist at the University of Hawaii who was not involved with the study, found the work impressive. “We know retrotransposons are at centromeres, but we don't know what their role is,” Presting said. “This starts to peel apart the different layers a little bit.”

“Being able to translate what we found in this easy model system to something that's harder to work on, is going to be very important,” Martienssen said. For example, the findings can aid in crop breeding or even understanding some cancers.

  1. Vongs A, et al. Science. 1993;260(5116):1926-1928.
  2. Slotkin RK, et al. Cell. 2009;136(3):461-472.
  3. Shimada A, et al. Nature Plants. 2024;10(9):1304-1316.