Long non-coding Satellite III RNAs link the heat shock response and cell proliferation

Genomes of complex organisms encode a wide variety of long non-coding RNAs (lncRNAs) that regulate gene expression. In human cells exposed to heat stress, transcription of lncRNAs is highly induced from Satellite III sequences located primarily within locus 9q12. Expression of Sat III transcripts is dependent on heat shock factor 1, the master regulator of the heat shock response. Sat III transcripts serve as the backbone of specific subnuclear structures called nuclear Stress Bodies, nSBs. Despite being known for two decades, the function of nSBs and Sat III transcripts is unknown, which prompted us to conduct RNA profiling in human cells where Sat III transcripts were either intact or downregulated. Comparison of these cells revealed that under stress conditions, Sat III transcripts are involved in regulating a plethora of genes, including such associated with cell growth and protein homeostasis. Our results show that the presence of Sat III transcripts has a repressive effect on cell proliferation. We propose a model in which the inducible expression of Sat III transcripts restrains cell proliferation, allowing the cell to assess whether to grow or undergo apoptosis, and thereby suggesting a function for these lncRNAs in cell fate decisions and in restoring protein homeostasis. Total RNA from HEK293T cells transfected with siRNA against Satellite III transcripts or scrambled siRNA and heat shocked 1 h at 42°C , or heat shocked 1 h at 42 °C followed by recovery for 6 h, or left untreated was compared.