The heat shock response is a conserved defense mechanism that protects cells from physiological stress, including thermal stress. Besides the activation of heat-shock-protein genes, the heat shock response is also known to bring about global suppression of transcription; however, the mechanism by which this occurs is poorly understood. One of the intriguing aspects of the heat shock response in human cells is the transcription of satellite-III (Sat3) long non-coding RNAs and their association with nuclear stress bodies (nSBs) of unknown function. Besides association with the Sat3 transcript, the nSBs are also known to recruit the transcription factors HSF1 and CREBBP, and several RNA-binding proteins, including the splicing factor SRSF1. We demonstrate here that the recruitment of CREBBP and SRSF1 to nSBs is Sat3-dependent, and that loss of Sat3 transcripts relieves the heat-shock-induced transcriptional repression of a few target genes. Conversely, forced expression of Sat3 transcripts results in the formation of nSBs and transcriptional repression even without a heat shock. Our results thus provide a novel insight into the regulatory role for the Sat3 transcripts in heat-shock-dependent transcriptional repression.
The authors declare no competing or financial interests.
A.G., S.S., R. Pandey, R. Parihar and G.C.M. performed the experiments; A.G., S.S., R. Pandey, M.M. and S.G. designed and analyzed the experiments; A.G., S.S. and S.G. conceived the study; A.G. and S.G. co-wrote the paper. S.G. coordinated the study. All authors analyzed the results and approved the final version of the manuscript.
This work was supported by a research grant (BT/PR11927/BRB/10/699/200) from the Department of Biotechnology, Ministry of Science and Technology (DBT), Government of India (to S.G.). A.G. and S.S. were supported by research fellowships from the Council of Scientific and Industrial Research (CSIR), Government of India and DBT, respectively.
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.189803.supplemental
- Received March 23, 2016.
- Accepted August 10, 2016.
- © 2016. Published by The Company of Biologists Ltd