Rajyalakshmi Meduri Research
Rajyalakshmi Meduri, PhD
Education:
BS, Mount Carmel College, Bangalore University, India, 2007
MS, Kasturba Medical College, Manipal University, India, 2010
PhD, University of Wuerzburg, Germany, 2016
Over the last decade much effort has been expended in understanding the role of DNA-DNA interactions in regulating gene expression. In particular, the role of chromatin loops in facilitating enhancer-promoter and promoter-terminator interactions has been studied. Three-dimensional genome architecture in mammals has been typically investigated in different cell types and disease states, and in yeast under normal growth conditions. In contrast, little work has been directed towards understanding the effect of environmental stress on specific gene-gene interactions and the biological significance of those interactions. However, our lab recently showed that in the model eukaryote S. cerevisiae (budding yeast), Heat Shock Protein (HSP) genes coalesce into foci in cells exposed to heat shock, and that these intergenic interactions are highly specific to genes regulated by the transcription factor HSF1 (Chowdhary, Kainth, et. al., Mol. Cell. Biol., 2017; Chowdhary, Kainth, et. al., Cell Reports, 2019). This intriguing finding was unveiled by employing high resolution Chromosome Conformation Capture (3C) and fluorescence microscopy in combination with powerful yeast genetics approaches.
Work conducted by Heike Krebber‘s lab, Göttingen, Germany, has revealed that in yeast exposed to heat shock, transcripts of housekeeping genes are retained in the nucleus while stress-specific mRNAs are preferentially exported to the cytoplasm (Zander et al. Nature 2016; Zander and Krebber, RNA Biology 2017). The authors proposed that stress-specific mRNAs achieve this by evading the quality control machinery, and that the nuclear export factor Mex67 plays a critical role [see Figure]. I am interested in understanding whether HSP gene coalescence has a role in the preferential export of HSP mRNAs.
In budding yeast, under non-stress conditions, adaptor proteins Hrb1, Gbp2, Nab2 and Npl3 bind to the nascent transcripts and ensure the proper maturation of the transcripts before they are exported by associating with Mex67-Mtr2 heterodimer. Under heat stress condition, the regular transcripts are retained in the nucleus. However, Mex67-Mtr2 directly binds to Hsf1 and Rpb1 to preferentially export the HSP mRNAs bypassing the quality control by the adaptor proteins. (Image and description from Zander et al, Nature 540: 593-596 (2016). Used with permission.)
