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MBC in Press, published online ahead of print March 23, 2005
Mol. Biol. Cell 10.1091/mbc.E04-12-1078

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Submitted on December 14, 2004
Revised on March 7, 2005
Accepted on March 15, 2005

Structural and Functional Characterization of Noncoding Repetitive RNAs Transcribed in Stressed Human Cells

Rut Valgardsdottir, Ilaria Chiodi, Manuela Giordano, Fabio Cobianchi, Silvano Riva, and Giuseppe Biamonti

Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy

Monitoring Editor: Joseph Gall

Thermal and chemical stresses induce the formation in human cells of novel and transient nuclear structures called nuclear stress bodies (nSBs). These contain heat shock factor 1 (HSF1) and a specific subset of pre-mRNA processing factors. Nuclear stress bodies are assembled on specific pericentromeric heterochromatic domains containing satellite III (SatIII) DNA. In response to stress these domains change their epigenetic status from heterochromatin to euchromatin, and are transcribed in poly-adenylated RNAs, that remain associated with nSBs. In this article we describe the cloning, sequencing and functional characterization of these transcripts. They are composed of SatIII repeats and originate from the transcription of multiple sites within the SatIII arrays. Interestingly, the level of SatIII RNAs can be down-regulated both by antisense oligonucleotides and small interfering RNAs (siRNA). Knock-down of SatIII RNA by siRNAs requires the activity of Argonaute 2 (Ago-2), a component of the RNA-induced silencing complex (RISC). Down-regulation of Satellite III RNAs significantly affects the recruitment of RNA processing factors to nSBs without altering the association of HSF1 with these structures nor the presence of acetylated histones within nSBs. Thus, Satellite III RNAs have a major role in the formation of nSBs.


Address correspondence to: Giuseppe Biamonti (biamonti{at}igm.cnr.it)




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