Formation Mechanism and Cellular Functions of Nuclear Stress Bodies Induced by Heat Stress

Abstract

Mammal possesses mechanisms that respond to environmental stresses, including heat, oxidation, radiation. Stress responses include cell death induction mechanism such as apoptosis and stress accommodation mechanism for survival. One of a major stress accommodation mechanism is formation of stress granules (SGs) and nuclear stress bodies (nSBs). SGs and nSBs, which are constituted by many proteins and RNAs, are reversible intracellular structures formed only when cells are exposed to environmental stresses. SGs, formed in the cytoplasm, have been found in a wide range of eukaryotes from yeast to humans. Intriguingly, nSBs, formed in the nucleus, have been found only in human cells. In this review, we focus on nSBs. nSBs were discovered in heat-stressed cells in 1989, and then many proteins and RNAs have been identified. Major components of nSBs are heat shock transcription factor family, splicing factors and non-coding RNAs (Satellite III RNA and initiator/elongator tRNA). Recently, many researchers have reported the formation mechanism of nSBs, however cellular functions of nSBs remain unclear. In this review, we introduce the basic researches focusing on the nSBs formation mechanism and cellular functions of nSBs constitution factors. heat stress, nuclear stress bodies, ribonucleoprotein (RNP) 生物は温熱，酸化，放射線といった環境ストレスに対して，ストレス応答が誘発される．ストレス応 答にはアポトーシスなどの細胞死誘導機構と生存のために働くストレス適応機構がある．生物は環境ス トレスの強弱により細胞死誘導機構とストレス適応機構を使い分けることで細胞の生死を決定し，個体 の恒常性を維持している． ストレス適応機構は，細胞周期の停止，翻訳抑制，HSPheat shock proteinsの発現上昇，RNA 分解， ストレス顆粒の形成など多岐にわたる 1-3) ．本稿では数あるストレス適応機構の中でもストレス顆粒に 注目する．RNA 結合タンパク質と RNA からなる凝集体であるストレス顆粒は，環境ストレスに曝さ れた時にのみ形成される可逆性の細胞内構造体であり，phase separation液相分離を経て形成される ことが報告されている 4) ．ストレス顆粒には，細胞質で形成されるストレス顆粒Stress granules: SGs と核内で形成される核内ストレス顆粒Nuclear stress bodies: nSBsの 2 種類が報告されている．SGs Nuclear stress bodies by heat stress Y. Miyoshi and K. Watanabe 23-