402 / 2019-02-23 09:43:19

Planting ideas for medicine: from thermal responses to human genetic diseases

thermomorphogenesis,RdDM,Histone Deacetylation,gene silencing,NMD

全体主题 > RNA Biology

Plants are highly sensitive to growth environment and even a change of 1ºC have major impacts on their growth and development. My lab has been at the forefront of elucidating molecular mechanisms that mediate environmental responses in plants and revealed a role for histone deacetylation as well as alternative splicing coupled with nonsense-mediated mRNA decay in thermal responses of plants (Tasset et al, PLoS Genetics, 2018; Sureshkumar et al, Nature Plants, 2016). In our pursuit of temperature responses, we discovered the first and only known triplet repeat expansion outside humans that is associated with a growth defect (Sureshkumar et al, Science, 2009). Triplet repeat expansions underlie several human genetic diseases such as Friedreich's ataxia, Huntington's disease and Fragile X syndrome. Among these diseases Friedreich's ataxia is caused by an intronic repeat expansion that some results in transcriptional down regulation. Although the underlying mutation in Friedreich's ataxia was known from 90s it was unclear how these repeat expansions result in transcriptional down regulation of the loci harbouring the expansion. Using the plant model, we have shown that triplet expansions lead to epigenetic silencing of the locus through a mechanism involving smallRNAs (Eimer et al, Cell, 2018). I will present our findings and also discuss some preliminary follow up work that has relevance for the treatment/management of Friedreich's ataxia.