Human satellite-III non-coding RNAs modulate heat-shock-induced transcriptional repression

Abstract

The heat shock response is a conserved defense mechanism that protects cells from physiological stress, including the thermal stress. Besides the activation of heat shock protein genes, the heat shock response is also known to bring about global suppression of transcription, the mechanism for which however is poorly understood. One of the intriguing aspects of the heat shock response in human cells is the transcription of Satellite-III (Sat3) long-noncoding RNAs and their association with nuclear stress bodies (nSBs) of unknown function. Besides the Sat3 transcript, the nSBs are also known to recruit 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 the transcriptional repression even without a heat shock. Our results thus provide a novel insight into the regulatory role for the Sat3 transcripts in the heat shock-dependent transcriptional repression.