The heat's on: nuclear stress bodies signal intron retention

Erhardt, Sylvia; Stoecklin, Georg

doi:10.15252/embj.2019104154

Cited by 13 publications

(8 citation statements)

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“…A common observation in diverse organisms has been the formation of stress granules triggered by adverse environmental conditions, whose composition is variable depending on the organism and on the stress condition [ 9 ]. The participation of stress TFs in the formation of some of these stress bodies has been reported, as is the case of human Hsf1 TF, which initiates the generation of nuclear stress bodies by interaction with pericentric tandem repeats leading to an increased transcription of large heterochromatic regions in response to stress [ 99 , 100 ]. The potential of stress IDTFs and other signaling IDPs to undergo LLPS, and their physicochemical characteristics allowing them to establish diverse protein and nucleic acid interactions, point them as components of stress bodies or condensates, even though its role in the control of transcription is still an open question.…”

Section: Resultsmentioning

confidence: 99%

Intrinsically disordered signaling proteins: Essential hub players in the control of stress responses in Saccharomyces cerevisiae

et al. 2022

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Cells have developed diverse mechanisms to monitor changes in their surroundings. This allows them to establish effective responses to cope with adverse environments. Some of these mechanisms have been well characterized in the budding yeast Saccharomyces cerevisiae, an excellent experimental model to explore and elucidate some of the strategies selected in eukaryotic organisms to adjust their growth and development in stressful conditions. The relevance of structural disorder in proteins and the impact on their functions has been uncovered for proteins participating in different processes. This is the case of some transcription factors (TFs) and other signaling hub proteins, where intrinsically disordered regions (IDRs) play a critical role in their function. In this work, we present a comprehensive bioinformatic analysis to evaluate the significance of structural disorder in those TFs (170) recognized in S. cerevisiae. Our findings show that 85.2% of these TFs contain at least one IDR, whereas ~30% exhibit a higher disorder level and thus were considered as intrinsically disordered proteins (IDPs). We also found that TFs contain a higher number of IDRs compared to the rest of the yeast proteins, and that intrinsically disordered TFs (IDTFs) have a higher number of protein-protein interactions than those with low structural disorder. The analysis of different stress response pathways showed a high content of structural disorder not only in TFs but also in other signaling proteins. The propensity of yeast proteome to undergo a liquid-liquid phase separation (LLPS) was also analyzed, showing that a significant proportion of IDTFs may undergo this phenomenon. Our analysis is a starting point for future research on the importance of structural disorder in yeast stress responses.

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Section: Resultsmentioning

confidence: 99%

Intrinsically disordered signaling proteins: Essential hub players in the control of stress responses in Saccharomyces cerevisiae

et al. 2022

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“…Interestingly, we previously found that heat stress alone caused cell death in an iPSC‐derived model of MNs. 16 Furthermore, heat stress, 49 , 50 ageing and neurodegeneration 51 , 52 , 53 all associate with intron retention. 2 , 4 , 54 , 55 Future research will investigate the molecular mechanisms by which elevated temperatures lead to similar responses as those observed in patient‐specific ALS MN cultures.…”

Section: Discussionmentioning

confidence: 99%

Image‐based deep learning reveals the responses of human motor neurons to stress and VCP‐related ALS

Verzat

Harley

Patani

et al. 2021

Neuropathology Appl Neurobio

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Aims Although morphological attributes of cells and their substructures are recognised readouts of physiological or pathophysiological states, these have been relatively understudied in amyotrophic lateral sclerosis (ALS) research. Methods In this study, we integrate multichannel fluorescence high‐content microscopy data with deep learning imaging methods to reveal—directly from unsegmented images—novel neurite‐associated morphological perturbations associated with (ALS‐causing) VCP‐mutant human motor neurons (MNs). Results Surprisingly, we reveal that previously unrecognised disease‐relevant information is withheld in broadly used and often considered ‘generic’ biological markers of nuclei (DAPI) and neurons ( β III‐tubulin). Additionally, we identify changes within the information content of ALS‐related RNA binding protein (RBP) immunofluorescence imaging that is captured in VCP‐mutant MN cultures. Furthermore, by analysing MN cultures exposed to different extrinsic stressors, we show that heat stress recapitulates key aspects of ALS. Conclusions Our study therefore reveals disease‐relevant information contained in a range of both generic and more specific fluorescent markers and establishes the use of image‐based deep learning methods for rapid, automated and unbiased identification of biological hypotheses.

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“…For example, the formation of SGs was proposed to be nucleated by specific protein-mRNA interaction that forms oligomers which are crosslinked by PABP-1 into microscopically visible SGs ( Anderson and Kedersha, 2008 ). Similarly, a number of nuclear bodies, including nucleolus, histone locus bodies (HLBs), Cajal body, Nuclear splicing speckles, paraspeckle, and nuclear stress bodies (nSB) were nucleated by specific RNAs which recruit additional proteins to form microscopically visible granules ( Mao et al, 2011 ; Shevtsov and Dundr, 2011 ; Falahati et al, 2016 ; Falahati and Wieschaus, 2017 ; Erhardt and Stoecklin, 2020 ). However, most of these condensates contain hundreds of proteins that their recruitment and interactions remain uncharacterized.…”

Section: The Biogenesis Of Membrane-less Condensatesmentioning

confidence: 99%

The Molecular and Functional Interaction Between Membrane-Bound Organelles and Membrane-Less Condensates

Zhou

2022

Front. Cell Dev. Biol.

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A major recent advance in cell biology is the mechanistic and kinetic understanding of biogenesis of many membrane-less condensates. As membrane-less condensates and membrane-bound organelles are two major approaches used by the eukaryotic cells to organize cellular contents, it is not surprising that these membrane-less condensates interact with the membrane-bound organelles and are dynamically regulated by the cellular signaling, metabolic states, and proteostasis network. In this review, I will discuss recent progress in the biogenesis of membrane-less condensates and their connections with well-studied membrane-bound organelles. Future work will reveal the molecular and functional connectome among different condensates and membrane-bound organelles.

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The heat's on: nuclear stress bodies signal intron retention

Cited by 13 publications

References 13 publications

Intrinsically disordered signaling proteins: Essential hub players in the control of stress responses in Saccharomyces cerevisiae

Intrinsically disordered signaling proteins: Essential hub players in the control of stress responses in Saccharomyces cerevisiae

Image‐based deep learning reveals the responses of human motor neurons to stress and VCP‐related ALS

The Molecular and Functional Interaction Between Membrane-Bound Organelles and Membrane-Less Condensates

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