| NUCLEAR STRESS BODIES REVEAL A LINK BETWEEN CHROMATIN ORGANIZATION AND DISTRIBUTION OF RNA PROCESSING FACTORS.
Biamonti G., Rizzi N., Chiodi I., Corioni M., Denegri M., Cobianchi F., Riva S.
Nuclear stress bodies are transient structures elicited by stress treatments such as heat shock or exposure to heavy metals. The assembly of these structures initiates with the recruitment of heat shock factor 1 (HSF1). Thereafter a subset of RNA processing factors, including hnRNP M, hnRNP HAP/SAF-B, ASF/SF2, SRp30c, Sam68, is recruited. Numerous data suggest that these bodies are not sites of transcription but rather depots for RNA molecules synthesized before stress. We have recently shown that the pericentromeric heterochromatic regions of human chromosome 9, 12 and 15 act as recruiting centers on which these structures are assembled. Surprisingly, stress bodies are not stained by DAPI or by antibodies against HP1, a typical marker of heterochromatin domains. In contrast, and unexpectedly, they are recognized by antibodies against the hyper-acetylated form of histone H4. In fact they correspond to the main sites of accumulation of this histone form in stressed cells. This result suggests that the higher order chromatin organization of heterochromatic regions of HSA9, 12 and 15 is drastically altered in response to stress, probably due to the recruitment of some, as yet unknown, histone acetylase by HSF1. In order to dissect the molecular mechanism underlying the formation of these structures we have determined the protein domain that mediates the recruitment of ASF/SF2. The recruitment depends on the second RRM of the protein. Amino acid substitutions that abrogate the recruitment also modify the activity of this factor in alternative splicing. A two-hybrid screening for proteins interacting with ASF/SF2 is currently in progress.
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