Nuclear stress bodies

Abstract

Nuclear stress bodies (nSBs) are unique subnuclear organelles which form in response to heat shock. They are initiated through a direct interaction between heat shock transcription factor 1 (HSF1) and pericentric tandem repeats of satellite III sequences and correspond to active transcription sites for noncoding satellite III transcripts. Given their unusual features, nSBs are distinct from other known transcription sites. In stressed cells, they are thought to participate in rapid, transient, and global reprogramming of gene expression through different types of mechanisms including chromatin remodeling and trapping of transcription and splicing factors. The analysis of these atypical and intriguing structures uncovers new facets of the relationship between nuclear organization and nuclear function.

Figure 1.

nSBs visualized with anti HSF1 and anti acetylated lysine antibodies. In unstressed cells (NHS), HSF1 (green labeling) displays a diffuse nucleocytoplasmic distribution. Upon heat-shock (HS), HSF1 is redistributed to a few nuclear foci, also known as stress granules, which form primarily on the 9q12 loci (indicated with arrow heads). An average of three copies of chromosome 9 are present in Hela cells. In heat-shocked cells, the 9q12 locus is enriched in acetylated histones. The binding of HSF1 is followed by the formation of acetylated foci, the recruitment of RNA polymerase II, the subsequent transcription of sat III repeats mainly into “G rich” transcripts, and the ultimate recruitment of splicing factors. (Bar scale = 5 µm).

Figure 2.

Schematic illustration of the possible roles of nSBs in heat-shocked cells. nSBs are thought to play a role in the cellular response to stress and cell protection. Three main hypotheses have been proposed which are not mutually exclusive: (A) Control of transcription and splicing activities. Upon heat-shock, sat III sequences and transcripts are thought to play a role in the control of transcriptional and splicing activities through sequestration of transcription and splicing factors (both represented as dots). Transient trapping of these factors could contribute to the shutdown or reprogramming of gene expression. It is also plausible that Sat III RNAs, by sequestering specific RNA-binding proteins into nSBs, may influence splicing decisions toward the synthesis of molecules involved in the cell defense to stress. (B) Regeneration of heterochromatin structure. In fission yeast, transcripts from pericentric regions play a role in the formation and maintenance of heterochromatin. In human cells, sat III transcripts may also play a role in protecting heterochromatic pericentric regions following heat-shock, either as long RNA molecules or as small RNA molecules generated by the RNAi machinery. (C) Transcriptional de-repression of genes located in the vicinity of nSBs through position effects. Loss of epigenetic repressive marks (red flags) at the 9q12 locus following heat shock could abolish the transcriptional repression exerted by pericentric heterochromatin on the activity of promoter genes present in cis (here visualized in brown and green) or possibly in trans (not shown) through chromatin opening and binding of transcription factors (TF).