Human Chromosomes 9, 12, and 15 Contain the Nucleation Sites of Stress-Induced Nuclear Bodies

Abstract

We previously reported the identification of a novel nuclear compartment detectable in heatshocked HeLa cells that we termed stress-induced Src-activated during mitosis nuclear body (SNB). This structure is the recruitment center for heat shock factor 1 and for a number of RNA processing factors, among a subset of Serine-Arginine splicing factors. In this article, we show that stress-induced SNBs are detectable in human but not in hamster cells. By means of hamsterϾhuman cell hybrids, we have identified three human chromosomes (9, 12, and 15) that are individually able to direct the formation of stress bodies in hamster cells. Similarly to stress-induced SNB, these bodies are sites of accumulation of hnRNP A1-interacting protein and heat shock factor 1, are usually associated to nucleoli, and consist of clusters of perichromatin granules. We show that the p13-q13 region of human chromosome 9 is sufficient to direct the formation of stress bodies in hamsterϾhuman cell hybrids. Fluorescence in situ hybridization experiments demonstrate that the pericentromeric heterochromatic q12 band of chromosome 9 and the centromeric regions of chromosomes 12 and 15 colocalize with stress-induced SNBs in human cells. Our data indicate that human chromosomes 9, 12, and 15 contain the nucleation sites of stress bodies in heat-shocked HeLa cells.

A key role for stress-induced satellite III transcripts in the relocalization of splicing factors into nuclear stress granules

“…One hypothesis is that the presence of splicing factors merely reflects the splicing of sat III transcripts, as strongly supported by our findings that sat III and hsp90α transcripts, but not the intronless hsp70 transcripts, are complexed with snRNPs in vivo. In this case, the particular composition of the splicing complexes present in the granules, containing some but not all splicing factors (Chiodi et al, 2000;Denegri et al, 2001;Denegri et al, 2002;Weighardt et al, 1999), might specify a certain type of transcript. Another possibility is that the binding of splicing factors to these transcripts plays a role in their stabilization.…”

“…Interestingly, certain splicing factors such as the hnRNP HAP and the serine/arginine-rich (SR) proteins 9G8, SF2/ASF and SRp30c have been shown to relocalize upon stress to nuclear stress granules, whereas others, such as small nuclear ribonucleoproteins (snRNPs) or SC35, do not, suggesting a possible mechanism to regulate splicing activity during stress by the sequestration of certain splicing factors within particular subnuclear regions (Chiodi et al, 2000;Denegri et al, 2001;Denegri et al, 2002;Weighardt et al, 1999).…”

Formation of nuclear stress granules involves HSF2 and coincides with the nucleolar localization of Hsp70

“…Furthermore, Mathew et al (Mathew et al, 2001) have reported that, in murine fibroblasts, HSF2 has the biochemical properties of a temperature-sensitive protein because, upon heat shock, HSF2 is localized to the perinuclear region, its solubility is decreased and DNA-binding activity is diminished. This intriguing difference between human and murine cells has also been observed with HSF1, because the stress-induced subnuclear compartmentalization of HSF1 has been detected only in human cells (Sarge et al, 1993;Denegri et al, 2002). Altogether, direct evidence of HSF2, human or murine, being a physiological transcriptional regulator of heat shock genes is missing.…”

“…Recently, stress granules were revealed to associate with human chromosome 9q11-q12, corresponding to a large block of heterochromatin composed primarily of satellite III repeats adjacent to the centromere (Jolly et al, 2002). Furthermore, Denegri et al (Denegri et al, 2002) have reported that, in addition to chromosome 9, chromosomes 12 and 15 also contain nucleation sites for stress granules. The functional significance of stress granules is still unknown.…”

Changes in the human nuclear chromatin induced by ultra wideband pulse irradiation

“…Within this locus, HSF1 binds through direct DNA-protein interaction with a nucleosome-containing subclass of satellite III repeats [20]. In addition to chromosome 9, chromosomes 12 and 15 also contain the nucleation sites of stress bodies in heat-shocked HeLa cells [21].…”