Heterogeneous nuclear ribonucleoprotein K inhibits heat shock-induced transcriptional activity of heat shock factor 1

Kim, Heejung; Lee, Jaejin; Cho, Jin-Hwan; Jeong, Jaeho; Park, A Young; Kang, Wonmo; Lee, Kong Joo

doi:10.1074/jbc.m117.774992

Cited by 13 publications

(5 citation statements)

References 43 publications

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“…Interestingly, a negative correlation between hnRNPK expression (a significant decrease) and hsp70 expression (a significant increase) was also observed in response to HS in the present study. The hnRNPK protein has also been reported to play a role in the heat shock response of cells and control expression of hsp70 mRNAs by inhibiting heat shock-induced transcriptional activity (Kim et al, 2017). Our present findings suggest that these splicing factors may organize a regulatory network of various groups of genes through AS as well as splicing inhibition to respond appropriately to a particular stress.…”

Section: Post-transcriptional Regulationsupporting

confidence: 52%

PacBio Isoform Sequencing and Illumina RNA Sequencing Provide Novel Insights on Responses to Acute Heat Stress in Apostichopus japonicus Coelomocytes

et al. 2022

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Significant increases in global sea surface temperatures are expected with climate change and may cause a serious challenge for marine organisms cultured in aquatic environments that are characterized by short and long-term fluctuations in water temperatures. Apostichopus japonicus, a sea cucumber with high nutritional value and pharmacological properties, is an important economic species that is widely raised in aquaculture in China. In recent years, continuous extreme high temperatures (up to 30°C) have occurred frequently in summer leading to mass mortality of sea cucumbers cultured in semi-open shallow regions seriously restricting the sustainable development of sea cucumber aquaculture. In the present study, we combined RNA-seq and PacBio single-molecular real-time (SMRT) sequencing technology to unveil the potential mechanisms of response to acute heat stress in A. japonicus coelomocytes. A total of 1,375 differentially expressed genes (DEGs) were identified in a comparison of control and 48 h heat stress (HS) groups. Pathway enrichment analysis indicated that nine important pathways induced by HS were significantly enriched (q-value < 0.05) and mostly fell into four classes: folding, sorting, and degradation, immune and infectious diseases, signal transduction, and post-transcriptional regulation. Among them, all 41 genes connected with protein processing in endoplasmic reticulum were significantly up-regulated, and 12 of these were selected and validated via qPCR. Furthermore, changes in alternative splicing (AS) were also identified in sea cucumbers following HS. A total of 1,224 and 1,251 differential alternative splicing (DAS) events were identified using splice junction counts (JC only) and reads on target and junction counts (JCEC) as the input for rMATS in CO-HS comparison. We further found that the RNA splicing-related genes were enriched in the spliceosome pathway and showed DAS in control versus heat-stressed animals. In particular, we compared and confirmed that the hsfs1 gene, the master regulator of the heat shock response, showed differentially spliced exons in response to HS. This is the first comprehensive study showing that transcriptional and post-transcriptional (AS) controls are involved in the acute heat stress response of sea cucumber coelomocytes and provides novel insights into the molecular mechanisms of echinoderm adaptation to environmental stress.

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Section: Post-transcriptional Regulationsupporting

confidence: 52%

PacBio Isoform Sequencing and Illumina RNA Sequencing Provide Novel Insights on Responses to Acute Heat Stress in Apostichopus japonicus Coelomocytes

et al. 2022

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“…Cysteine residues of hnRNPs are often found oxidized 46 and are known to be susceptible to electrophile adduction, especially within RNA recognition motifs 47 . Specifically, the thiol redox state of hnRNP K has been reported to modulate the heat shock response 48 , supporting the idea that hnRNP thiol modifications can play adaptive regulatory roles. Another cluster of MPST target proteins is organized around vimentin.…”

Section: Discussionmentioning

confidence: 69%

3-Mercaptopyruvate sulfur transferase is a protein persulfidase

et al. 2023

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Protein S-persulfidation (P-SSH) is recognized as a common posttranslational modification. It occurs under basal conditions and is often observed to be elevated under stress conditions. However, the mechanism(s) by which proteins are persulfidated inside cells have remained unclear. Here we report that 3-mercaptopyruvate sulfur transferase (MPST) engages in direct protein-to-protein transpersulfidation reactions beyond its previously known protein substrates thioredoxin and MOCS3/Uba4, associated with H2S generation and transfer RNA thiolation, respectively. We observe that depletion of MPST in human cells lowers overall intracellular protein persulfidation levels and identify a subset of proteins whose persulfidation depends on MPST. The predicted involvement of these proteins in the adaptation to stress responses supports the notion that MPST-dependent protein persulfidation promotes cytoprotective functions. The observation of MPST-independent protein persulfidation suggests that other protein persulfidases remain to be identified.

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“…The actions of hnRNPs also change depending on their oxidation status. For example, the activity of hnRNPk (a chaperone and inhibitor of HSF1 binding to heat shock elements) alters depending on the oxidation status of a single redox‐sensitive cysteine residue, affecting the activation of heat shock response genes (Kim et al ., ). Alternatively, epigenetic processes may be mediated by the CaRe‐responsive signalling pathways detailed above.…”

Section: Connections Between Care Status and Sex Determinationmentioning

confidence: 97%

Cellular calcium and redox regulation: the mediator of vertebrate environmental sex determination?

et al. 2020

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Many reptiles and some fish determine offspring sex by environmental cues such as incubation temperature. The mechanism by which environmental signals are captured and transduced into specific sexual phenotypes has remained unexplained for over 50 years. Indeed, environmental sex determination (ESD) has been viewed as an intractable problem because sex determination is influenced by a myriad of genes that may be subject to environmental influence. Recent demonstrations of ancient, conserved epigenetic processes in the regulatory response to environmental cues suggest that the mechanisms of ESD have a previously unsuspected level of commonality, but the proximal sensor of temperature that ultimately gives rise to one sexual phenotype or the other remains unidentified. Here, we propose that in ESD species, environmental cues are sensed by the cell through highly conserved ancestral elements of calcium and redox (CaRe) status, then transduced to activate ubiquitous signal transduction pathways, or influence epigenetic processes, ultimately to drive the differential expression of sex genes. The early evolutionary origins of CaRe regulation, and its essential role in eukaryotic cell function, gives CaRe a propensity to be independently recruited for diverse roles as a 'cellular sensor' of environmental conditions. Our synthesis provides the first cohesive mechanistic model connecting environmental signals and sex determination pathways in vertebrates, providing direction and a framework for developing targeted experimentation.

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Heterogeneous nuclear ribonucleoprotein K inhibits heat shock-induced transcriptional activity of heat shock factor 1

Cited by 13 publications

References 43 publications

PacBio Isoform Sequencing and Illumina RNA Sequencing Provide Novel Insights on Responses to Acute Heat Stress in Apostichopus japonicus Coelomocytes

PacBio Isoform Sequencing and Illumina RNA Sequencing Provide Novel Insights on Responses to Acute Heat Stress in Apostichopus japonicus Coelomocytes

3-Mercaptopyruvate sulfur transferase is a protein persulfidase

Cellular calcium and redox regulation: the mediator of vertebrate environmental sex determination?

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