Auxin-Inducible Degron System Reveals Temporal-Spatial Roles of HSF-1 and Its Transcriptional Program in Lifespan Assurance.
Auxin-Inducible Degron System Reveals Temporal-Spatial Roles of HSF-1 and Its Transcriptional Program in Lifespan Assurance.
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DOI：
10.3389/fragi.2022.899744
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发表时间：
2022
影响因子：
--
通讯作者：
Li, Jian
中科院分区：
文献类型：
--
作者：
Morphis, Allison C.;Edwards, Stacey L.;Erdenebat, Purevsuren;Kumar, Lalit;Li, Jian
关键词：
HSF-1是细胞蛋白毒性应激反应的关键调节因子，是动物寿命所必需的。在秀丽隐杆线虫中，HSF-1介导的热休克反应（HSR）在成虫的第一天急剧下降，根据RNAi研究，HSF-1主要在幼虫期发挥作用，以保证寿命。然而，在生命周期中组织对HSF-1的需求尚不清楚。利用生长素诱导退化（AID）系统，我们成功地解开了HSF-1在发育和寿命中的作用。在野生型动物中，我们发现HSF-1在整个生命周期内都是必需的。这一时期延长了长寿动物的生殖系干细胞（GSC）阻滞或胰岛素/IGF-1信号（IIS）减少。虽然在发育过程中，任何主要体细胞组织中HSF-1的消耗都会导致严重的缺陷，但HSF-1主要在肠道和可能的神经系统中发挥作用，以维持成年人的寿命。最后，通过结合AID和全基因组转录分析，我们发现HSF-1在成年早期直接激活组成性表达的伴侣和共同伴侣基因的转录，这是其在长寿保障中的作用的基础。
HSF-1 is a key regulator of cellular proteotoxic stress response and is required for animal lifespan. In C. elegans, HSF-1 mediated heat shock response (HSR) declines sharply on the first day of adulthood, and HSF-1 was proposed to function primarily during larval stages for lifespan assurance based on studies using RNAi. The tissue requirement for HSF-1 in lifespan, however, is not well understood. Using the auxin-inducible degron (AID) system, we manage to uncouple the roles of HSF-1 in development and longevity. In wild-type animals, we find HSF-1 is required during the whole self-reproductive period for lifespan. This period is extended in long-lived animals that have arrested germline stem cells (GSC) or reduced insulin/IGF-1 signaling (IIS). While depletion of HSF-1 from any major somatic tissues during development results in severe defects, HSF-1 primarily functions in the intestine and likely neural system of adults to support lifespan. Finally, by combining AID and genome-wide transcriptional analyses, we find HSF-1 directly activates the transcription of constitutively-expressed chaperone and co-chaperone genes among others in early adulthood, which underlies its roles in longevity assurance.
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影响因子：
3.3
作者：
Higuchi-Sanabria R;Paul JW 3rd;Durieux J;Benitez C;Frankino PA;Tronnes SU;Garcia G;Daniele JR;Monshietehadi S;Dillin A
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作者：
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