Genetics of triplet repeat expansions

Genomes of organisms have several types of repeat sequences. One subset of repeats are microsatellite repeats (2-6bp long) that are present in almost all organisms. Repeat sequences are more prone to error and thus are highly variable among individuals within a population. The dynamic nature of repeat sequences results in massive variations, with the extreme examples of expansions that can lead to disease. Almost 50 different neurogenetic disorders occur due to repeat expansions in humans. We have discovered a an intronic triplet repeat expansion in Arabidopsis thaliana and are exploiting this system to work out the molecular mechanisms mediating triplet expansion associated phenotypic diversification. 

Relevant Key Publication: 

1.  Sureshkumar, S*., Todesco, M*., Schneeberger, K., Harilal, R., Balasubramanian, S and Weigel, D (2009) A genetic defect caused by a triplet repeat expansion in Arabidopsis thaliana. Science, 323(5917):1060-1063


Protein modifications in epigenetic silencing

Triplet repeat expansions can occur any where in a gene (e.g., coding or noncoding regions). Expansions in coding regions can affect the encoded protein. The expansion in Arabidopsis Bur-0 accession is an intronic repeat expansion, similar to the one in Friedreich's ataxia cause epigenetic silencing. We have recently worked out the molecular mechanism of epigenetic silencing in the plant model. We have uncovered several genes associated with this response. In addition, we have carried out a suppressor screen and identified factors that are critical for epigenetic silencing. Our findings reveal a role for protein modifications such as methylation, acetylation and desumoylation in epigenetic silencing and we are currently working out the molecular mechanisms. 

Relevant Key Publication:

1. Eimer, H*., Sureshkumar, S*., Singh Yadav, A., Kraupner-Taylor, C., Bandaranayake, C., Seleznev, A., Thomason, T., Fletcher, SJ., Gordon, SF., Carroll, BJ and Balasubramanian, S (2018) RNA dependent epigenetic silencing directs transcriptional down regulation caused by intronic repeat expansions, Cell, 174(5) : 1095-1105. 


Natural variation in environmental responses

Another key area of our work involves exploiting natural variation to understand how plants respond to changes in the environment. Particularly, we are interested in how molecular mechanisms such as epigenetic changes (e.g., histone modifications, DNA methylation etc) or splicing are modified to regulate specific environmental responses in plants. For example, we have recently shown that increase in temperatures lead to alternative splicing coupled with nonsense-mediated mRNA decay (AS-NMD) of  FLOWERING LOCUS M (FLM), which in turn affect temperature-induced flowering response in Arabidopsis. We are interested in exploring this in canola, one of the key Australian crop plant. 

Relevant Key Publication: 

1. Sureshkumar, S., Dent, C., Seleznev, A., Tasset, C and Balasubramanian, S (2016) Nonsense-mediated mRNA decay modulates FLM-dependent thermosensory flowering response in Arabidopsis, Nature Plants, 2(5):16055