Heat Shock-Induced Transcriptional and Translational Arrest in Mammalian Cells

Goenka, Anshika; Parihar, Rashmi; Ganesh, Subramaniam

doi:10.1007/978-3-319-90725-3_12

Cited by 4 publications

(5 citation statements)

References 106 publications

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“…E. coli HflX was later found to possess an intrinsic ribosomesplitting activity, capable of disassembling vacant as well as certain mRNA-containing 70S ribosomes into subunits (Coatham et al, 2016; Zhang et al, 2015). The heat shock is known to induce pausing of translating ribosomes at early elongation steps in both eukaryotes and prokaryotes (Goenka et al, 2018; Shalgi et al, 2013; Zhang et al, 2017), which frequently resulted in the formation of non-productive, stalled ribosomes through various mechanisms (Doma and Parker, 2006; Hayes and Sauer, 2003). Therefore, HflX was proposed to be responsible for splitting and recycling stalled non-productive 70S ribosomal complexes accumulated under heat-shock conditions (Zhang et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Cryo-EM Structure of the 50S-HflX Complex Reveals a Novel Mechanism of Antibiotic Resistance inE. coli

Dai

Gao

2022

Preprint

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Bacterial HflX is a conserved ribosome-binding GTPase involved in splitting ribosomal complexes accumulated under stress condition. However, the atomic details of its ribosomal interaction remain to be elucidated. In this work, we present a high-resolution structure of the E. coli 50S subunit bound with HflX. The structure reveals highly specific contacts between HflX and the ribosomal RNA, and in particular, an insertion loop of the N-terminal domain of HflX is situated in the peptidyl transferase center (PTC) and makes direct interactions with PTC residues. Interestingly, this loop displays steric clash with a few PTC-targeting antibiotics on the 50S subunit, such as chloramphenicol. Deletion of hflX results in hypersensitivity to chloramphenicol treatment, and a loop residue G154 of HflX is important for the observed chloramphenicol resistance. Overall, our results suggest that HflX could be a general stress response factor that functions in both stalled ribosome splitting and PTC antibiotic displacing.

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Section: Introductionmentioning

confidence: 99%

Cryo-EM Structure of the 50S-HflX Complex Reveals a Novel Mechanism of Antibiotic Resistance inE. coli

Dai

Gao

2022

Preprint

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Section: Introductionmentioning

confidence: 99%

“…The heat shock response is a conserved mechanism in the eukaryotes whereby the cells mount a defensive response against various environmental, physical and chemical stressors such as increased temperature, oxidative stress and heavy metals (Goenka et al, 2018). One of the major classes of effectors of this defense response is the chaperoning activity of heat shock proteins (HSPs) (Goenka et al, 2018). During the stress, the genes encoding HSPs are transcriptionally activated by heat shock transcription factor 1 (HSF1), which directly binds to the heat shock element (HSE) present in promoters of the HSP genes (Goenka et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…One of the major classes of effectors of this defense response is the chaperoning activity of heat shock proteins (HSPs) (Goenka et al, 2018). During the stress, the genes encoding HSPs are transcriptionally activated by heat shock transcription factor 1 (HSF1), which directly binds to the heat shock element (HSE) present in promoters of the HSP genes (Goenka et al, 2018). However, the specific trigger that activates HSF1 during heat stress is still unclear.…”

Section: Introductionmentioning

confidence: 99%

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Perinuclear mitochondrial clustering, increased ROS levels, and HIF1 are required for the activation of HSF1 by heat stress

Agarwal

Ganesh

2020

Journal of Cell Science

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The heat shock response (HSR) is a conserved cellular defensive response against stresses such as temperature, oxidative stress and heavy metals. A significant group of players in the HSR is the set of molecular chaperones known as heat shock proteins (HSPs), which assist in the refolding of unfolded proteins and prevent the accumulation of damaged proteins. HSP genes are activated by the HSF1 transcription factor, a master regulator of the HSR pathway. A variety of stressors activate HSF1, but the key molecular players and the processes that directly contribute to HSF1 activation remain unclear. In this study, we show that heat shock induces perinuclear clustering of mitochondria in mammalian cells, and this clustering is essential for activation of the HSR. We also show that this perinuclear clustering of mitochondria results in increased levels of reactive oxygen species in the nucleus, leading to the activation of hypoxiainducible factor-1α (HIF-1α). To conclude, we provide evidence to suggest that HIF-1α is one of the crucial regulators of HSF1 and that HIF-1α is essential for activation of the HSR during heat shock.

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“…In the past several years, lncRNAs have been found to affect gene expression in various biological and physiopathological conditions involving neurodegeneration, cellular stress response, and cancer [ 76 , 77 , 78 , 79 ]. These RNA molecules which are >200 nt in length, generally lack protein-coding capacity and mostly contain the 5′m7G caps and 3′ poly(A) tails structures like mRNAs; however, they are more dynamic and tissue-specific compared to mRNAs, thus suggesting they play multiple functional roles [ 80 ].…”

Section: Long Non-coding Rnasmentioning

confidence: 99%

The Role of Non-Coding RNAs in Glioma

et al. 2022

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For decades, research in cancer biology has been focused on the protein-coding fraction of the human genome. However, with the discovery of non-coding RNAs (ncRNAs), it has become known that these entities not only function in numerous fundamental life processes such as growth, differentiation, and development, but also play critical roles in a wide spectrum of human diseases, including cancer. Dysregulated ncRNA expression is found to affect cancer initiation, progression, and therapy resistance, through transcriptional, post-transcriptional, or epigenetic processes in the cell. In this review, we focus on the recent development and advances in ncRNA biology that are pertinent to their role in glioma tumorigenesis and therapy response. Gliomas are common, and are the most aggressive type of primary tumors, which account for ~30% of central nervous system (CNS) tumors. Of these, glioblastoma (GBM), which are grade IV tumors, are the most lethal brain tumors. Only 5% of GBM patients survive beyond five years upon diagnosis. Hence, a deeper understanding of the cellular non-coding transcriptome might help identify biomarkers and therapeutic agents for a better treatment of glioma. Here, we delve into the functional roles of microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) in glioma tumorigenesis, discuss the function of their extracellular counterparts, and highlight their potential as biomarkers and therapeutic agents in glioma.

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Heat Shock-Induced Transcriptional and Translational Arrest in Mammalian Cells

Cited by 4 publications

References 106 publications

Cryo-EM Structure of the 50S-HflX Complex Reveals a Novel Mechanism of Antibiotic Resistance inE. coli

Cryo-EM Structure of the 50S-HflX Complex Reveals a Novel Mechanism of Antibiotic Resistance inE. coli

Perinuclear mitochondrial clustering, increased ROS levels, and HIF1 are required for the activation of HSF1 by heat stress

The Role of Non-Coding RNAs in Glioma

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