Pub Date : 2024-09-08DOI: 10.1016/j.celrep.2024.114695
Caroline Thivierge, Maxime Bellefeuille, Sarah-Slim Diwan, Boris J.A. Dyakov, Rania Leventis, Gabrielle Perron, Hamed S. Najafabadi, Simon-Pierre Gravel, Anne-Claude Gingras, Thomas F. Duchaine
MicroRNAs (miRNAs) play crucial roles in physiological functions and disease, but the regulation of their nuclear biogenesis remains poorly understood. Here, BioID on Drosha, the catalytic subunit of the microprocessor complex, reveals its proximity to splicing factor proline- and glutamine (Q)-rich (SFPQ), a multifunctional RNA-binding protein (RBP) involved in forming paraspeckle nuclear condensates. SFPQ depletion impacts both primary and mature miRNA expression, while other paraspeckle proteins (PSPs) or the paraspeckle scaffolding RNA NEAT1 do not, indicating a paraspeckle-independent role. Comprehensive transcriptomic analyses show that SFPQ loss broadly affects RNAs and miRNA host gene (HG) expression, influencing both their transcription and the stability of their products. Notably, SFPQ protects the oncogenic miR-17∼92 polycistron from degradation by the nuclear exosome targeting (NEXT)-exosome complex and is tightly linked with its overexpression across a broad variety of cancers. Our findings reveal a dual role for SFPQ in regulating miRNA HG transcription and stability, as well as its significance in cancers.
{"title":"Paraspeckle-independent co-transcriptional regulation of nuclear microRNA biogenesis by SFPQ","authors":"Caroline Thivierge, Maxime Bellefeuille, Sarah-Slim Diwan, Boris J.A. Dyakov, Rania Leventis, Gabrielle Perron, Hamed S. Najafabadi, Simon-Pierre Gravel, Anne-Claude Gingras, Thomas F. Duchaine","doi":"10.1016/j.celrep.2024.114695","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114695","url":null,"abstract":"<p>MicroRNAs (miRNAs) play crucial roles in physiological functions and disease, but the regulation of their nuclear biogenesis remains poorly understood. Here, BioID on Drosha, the catalytic subunit of the microprocessor complex, reveals its proximity to splicing factor proline- and glutamine (Q)-rich (SFPQ), a multifunctional RNA-binding protein (RBP) involved in forming paraspeckle nuclear condensates. SFPQ depletion impacts both primary and mature miRNA expression, while other paraspeckle proteins (PSPs) or the paraspeckle scaffolding RNA <em>NEAT1</em> do not, indicating a paraspeckle-independent role. Comprehensive transcriptomic analyses show that SFPQ loss broadly affects RNAs and miRNA host gene (HG) expression, influencing both their transcription and the stability of their products. Notably, SFPQ protects the oncogenic miR-17∼92 polycistron from degradation by the nuclear exosome targeting (NEXT)-exosome complex and is tightly linked with its overexpression across a broad variety of cancers. Our findings reveal a dual role for SFPQ in regulating miRNA HG transcription and stability, as well as its significance in cancers.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1016/j.celrep.2024.114730
Alex M Francette, Karen M Arndt
The polymerase-associated factor 1 (Paf1) complex (Paf1C) is a conserved protein complex with critical functions during eukaryotic transcription. Previous studies showed that Paf1C is multi-functional, controlling specific aspects of transcription ranging from RNA polymerase II (RNAPII) processivity to histone modifications. However, it is unclear how specific Paf1C subunits directly impact transcription and coupled processes. We have compared conditional depletion to steady-state deletion for each Paf1C subunit to determine the direct and indirect contributions to gene expression in Saccharomyces cerevisiae. Using nascent transcript sequencing, RNAPII profiling, and modeling of transcription elongation dynamics, we have demonstrated direct effects of Paf1C subunits on RNAPII processivity and elongation rate and indirect effects on transcript splicing and repression of antisense transcripts. Further, our results suggest that the direct transcriptional effects of Paf1C cannot be readily assigned to any particular histone modification. This work comprehensively analyzes both the immediate and the extended roles of each Paf1C subunit in transcription elongation and transcript regulation.
{"title":"Multiple direct and indirect roles of the Paf1 complex in transcription elongation, splicing, and histone modifications.","authors":"Alex M Francette, Karen M Arndt","doi":"10.1016/j.celrep.2024.114730","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114730","url":null,"abstract":"<p><p>The polymerase-associated factor 1 (Paf1) complex (Paf1C) is a conserved protein complex with critical functions during eukaryotic transcription. Previous studies showed that Paf1C is multi-functional, controlling specific aspects of transcription ranging from RNA polymerase II (RNAPII) processivity to histone modifications. However, it is unclear how specific Paf1C subunits directly impact transcription and coupled processes. We have compared conditional depletion to steady-state deletion for each Paf1C subunit to determine the direct and indirect contributions to gene expression in Saccharomyces cerevisiae. Using nascent transcript sequencing, RNAPII profiling, and modeling of transcription elongation dynamics, we have demonstrated direct effects of Paf1C subunits on RNAPII processivity and elongation rate and indirect effects on transcript splicing and repression of antisense transcripts. Further, our results suggest that the direct transcriptional effects of Paf1C cannot be readily assigned to any particular histone modification. This work comprehensively analyzes both the immediate and the extended roles of each Paf1C subunit in transcription elongation and transcript regulation.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1016/j.celrep.2024.114720
Clément Blot, Mathilde Lavernhe, Geanncarlo Lugo-Villarino, Kimberley Coulson, Marie Salon, Margot Tertrais, Rémi Planès, Karin Santoni, Hélène Authier, Godefroy Jacquemin, Mouna Rahabi, Mélissa Parny, Isabelle Raymond Letron, Etienne Meunier, Lise Lefèvre, Agnès Coste
Macrophages are major host cells for the protozoan Leishmania parasite. Depending on their activation state, they either contribute to the detection and elimination of Leishmania spp. or promote parasite resilience. Here, we report that the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages plays a pivotal role in the progression of Leishmania infantum infection by controlling inflammation and redox balance of macrophages. We also highlight the involvement of the NOX2/reactive oxygen species (ROS) axis in early Nrf2 activation and, subsequently, prostaglandin E2 (PGE2)/EP2r signaling in the sustenance of Nrf2 activation upon infection. Moreover, we establish a ferroptosis-like process within macrophages as a cell death program of L. infantum and the protective effect of Nrf2 in macrophages against L. infantum death. Altogether, these results identify Nrf2 as a critical factor for the susceptibility of L. infantum infection, highlighting Nrf2 as a promising pharmacological target for the development of therapeutic approaches for the treatment of visceral leishmaniasis.
{"title":"Leishmania infantum exploits the anti-ferroptosis effects of Nrf2 to escape cell death in macrophages.","authors":"Clément Blot, Mathilde Lavernhe, Geanncarlo Lugo-Villarino, Kimberley Coulson, Marie Salon, Margot Tertrais, Rémi Planès, Karin Santoni, Hélène Authier, Godefroy Jacquemin, Mouna Rahabi, Mélissa Parny, Isabelle Raymond Letron, Etienne Meunier, Lise Lefèvre, Agnès Coste","doi":"10.1016/j.celrep.2024.114720","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114720","url":null,"abstract":"<p><p>Macrophages are major host cells for the protozoan Leishmania parasite. Depending on their activation state, they either contribute to the detection and elimination of Leishmania spp. or promote parasite resilience. Here, we report that the activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in macrophages plays a pivotal role in the progression of Leishmania infantum infection by controlling inflammation and redox balance of macrophages. We also highlight the involvement of the NOX2/reactive oxygen species (ROS) axis in early Nrf2 activation and, subsequently, prostaglandin E2 (PGE2)/EP2r signaling in the sustenance of Nrf2 activation upon infection. Moreover, we establish a ferroptosis-like process within macrophages as a cell death program of L. infantum and the protective effect of Nrf2 in macrophages against L. infantum death. Altogether, these results identify Nrf2 as a critical factor for the susceptibility of L. infantum infection, highlighting Nrf2 as a promising pharmacological target for the development of therapeutic approaches for the treatment of visceral leishmaniasis.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1016/j.celrep.2024.114708
Philip J M Brouwer, Hailee R Perrett, Tim Beaumont, Haye Nijhuis, Sabine Kruijer, Judith A Burger, Ilja Bontjer, Wen-Hsin Lee, James A Ferguson, Martin Schauflinger, Helena Müller-Kräuter, Rogier W Sanders, Thomas Strecker, Marit J van Gils, Andrew B Ward
Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccine candidates have generally been unsuccessful at doing so, and the associated antibody responses to these vaccines remain poorly characterized. Here, we establish an electron microscopy-based epitope mapping workflow that enables high-resolution structural characterization of polyclonal antibodies to the GPC. By applying this method to rabbits vaccinated with a recombinant GPC vaccine and a GPC-derived virus-like particle, we reveal determinants of neutralization that involve epitopes of the GPC-A competition cluster. Furthermore, by identifying undescribed immunogenic off-target epitopes, we expose the challenges that recombinant GPC vaccines face. By enabling detailed polyclonal antibody characterization, our work ushers in a next generation of more rational Lassa vaccine design.
{"title":"Defining bottlenecks and opportunities for Lassa virus neutralization by structural profiling of vaccine-induced polyclonal antibody responses.","authors":"Philip J M Brouwer, Hailee R Perrett, Tim Beaumont, Haye Nijhuis, Sabine Kruijer, Judith A Burger, Ilja Bontjer, Wen-Hsin Lee, James A Ferguson, Martin Schauflinger, Helena Müller-Kräuter, Rogier W Sanders, Thomas Strecker, Marit J van Gils, Andrew B Ward","doi":"10.1016/j.celrep.2024.114708","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114708","url":null,"abstract":"<p><p>Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccine candidates have generally been unsuccessful at doing so, and the associated antibody responses to these vaccines remain poorly characterized. Here, we establish an electron microscopy-based epitope mapping workflow that enables high-resolution structural characterization of polyclonal antibodies to the GPC. By applying this method to rabbits vaccinated with a recombinant GPC vaccine and a GPC-derived virus-like particle, we reveal determinants of neutralization that involve epitopes of the GPC-A competition cluster. Furthermore, by identifying undescribed immunogenic off-target epitopes, we expose the challenges that recombinant GPC vaccines face. By enabling detailed polyclonal antibody characterization, our work ushers in a next generation of more rational Lassa vaccine design.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1016/j.celrep.2024.114753
Panagiotis Mistriotis
Panagiotis Mistriotis spoke with Luca Gasparoli about his scientific journey and inspiration to become a scientist and his focus on investigating the mechanisms underlying mechanical regulation of cell migration, stem cell fate decisions, and smooth muscle cell function; in particular, he discussed his lab’s recent publication in Cell Reports exploring how spatial confinement influences migrating cells’ response to fluid flow.
{"title":"Q&A with Panagiotis Mistriotis","authors":"Panagiotis Mistriotis","doi":"10.1016/j.celrep.2024.114753","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114753","url":null,"abstract":"<p>Panagiotis Mistriotis spoke with Luca Gasparoli about his scientific journey and inspiration to become a scientist and his focus on investigating the mechanisms underlying mechanical regulation of cell migration, stem cell fate decisions, and smooth muscle cell function; in particular, he discussed his lab’s <span><span>recent publication in <em>Cell Reports</em></span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> exploring how spatial confinement influences migrating cells’ response to fluid flow.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1016/j.celrep.2024.114701
Dahlia Kushinsky, Emmanouil Tsivourakis, Daniella Apelblat, Ori Roethler, Mor Breger-Mikulincer, Katayun Cohen-Kashi Malina, Ivo Spiegel
Balancing plasticity and stability in neural circuits is essential for an animal's ability to learn from its environment while preserving proper processing and perception of sensory information. However, unlike the mechanisms that drive plasticity in neural circuits, the activity-induced molecular mechanisms that convey functional stability remain poorly understood. Focusing on the visual cortex of adult mice and combining transcriptomics, electrophysiology, and in vivo calcium imaging, we find that the daily appearance of light induces, in excitatory neurons, a large gene program along with rapid and transient increases in the ratio of excitation and inhibition (E/I ratio) and neural activity. Furthermore, we find that the light-induced transcription factor NPAS4 drives these daily normalizations of the E/I ratio and neural activity rates and that it stabilizes the neurons' response properties. These findings indicate that daily sensory-induced transcription normalizes the E/I ratio and drives downward firing rate homeostasis to maintain proper sensory processing and perception.
{"title":"Daily light-induced transcription in visual cortex neurons drives downward firing rate homeostasis and stabilizes sensory processing.","authors":"Dahlia Kushinsky, Emmanouil Tsivourakis, Daniella Apelblat, Ori Roethler, Mor Breger-Mikulincer, Katayun Cohen-Kashi Malina, Ivo Spiegel","doi":"10.1016/j.celrep.2024.114701","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114701","url":null,"abstract":"<p><p>Balancing plasticity and stability in neural circuits is essential for an animal's ability to learn from its environment while preserving proper processing and perception of sensory information. However, unlike the mechanisms that drive plasticity in neural circuits, the activity-induced molecular mechanisms that convey functional stability remain poorly understood. Focusing on the visual cortex of adult mice and combining transcriptomics, electrophysiology, and in vivo calcium imaging, we find that the daily appearance of light induces, in excitatory neurons, a large gene program along with rapid and transient increases in the ratio of excitation and inhibition (E/I ratio) and neural activity. Furthermore, we find that the light-induced transcription factor NPAS4 drives these daily normalizations of the E/I ratio and neural activity rates and that it stabilizes the neurons' response properties. These findings indicate that daily sensory-induced transcription normalizes the E/I ratio and drives downward firing rate homeostasis to maintain proper sensory processing and perception.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1016/j.celrep.2024.114707
Zachary W Davis, Alexandra Busch, Christopher Steward, Lyle Muller, John Reynolds
Intrinsic cortical activity forms traveling waves that modulate sensory-evoked responses and perceptual sensitivity. These intrinsic traveling waves (iTWs) may arise from the coordination of synaptic activity through long-range feature-dependent horizontal connectivity within cortical areas. In a spiking network model that incorporates feature-selective patchy connections, we observe iTW motifs that result from shifts in excitatory/inhibitory balance as action potentials traverse these patchy connections. To test whether feature-selective motifs occur in vivo, we examined data recorded in the middle temporal visual area (Area MT) of marmosets performing a visual detection task. We find that some iTWs form motifs that are feature selective, exhibiting direction-selective modulations in spiking activity. Further, motifs modulate the gain of target-evoked responses and perceptual sensitivity if the target matches the preference of the motif. These results suggest that iTWs are shaped by the patchy horizontal fiber projections in the cortex and can regulate neural and perceptual sensitivity in a feature-selective manner.
{"title":"Horizontal cortical connections shape intrinsic traveling waves into feature-selective motifs that regulate perceptual sensitivity.","authors":"Zachary W Davis, Alexandra Busch, Christopher Steward, Lyle Muller, John Reynolds","doi":"10.1016/j.celrep.2024.114707","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114707","url":null,"abstract":"<p><p>Intrinsic cortical activity forms traveling waves that modulate sensory-evoked responses and perceptual sensitivity. These intrinsic traveling waves (iTWs) may arise from the coordination of synaptic activity through long-range feature-dependent horizontal connectivity within cortical areas. In a spiking network model that incorporates feature-selective patchy connections, we observe iTW motifs that result from shifts in excitatory/inhibitory balance as action potentials traverse these patchy connections. To test whether feature-selective motifs occur in vivo, we examined data recorded in the middle temporal visual area (Area MT) of marmosets performing a visual detection task. We find that some iTWs form motifs that are feature selective, exhibiting direction-selective modulations in spiking activity. Further, motifs modulate the gain of target-evoked responses and perceptual sensitivity if the target matches the preference of the motif. These results suggest that iTWs are shaped by the patchy horizontal fiber projections in the cortex and can regulate neural and perceptual sensitivity in a feature-selective manner.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1016/j.celrep.2024.114754
Cameron G Williams, Marcela L Moreira, Takahiro Asatsuma, Hyun Jae Lee, Shihan Li, Thomas N Burn, Irving Barrera, Evan Murray, Megan S F Soon, Jessica A Engel, David S Khoury, Shirley Le, Brooke J Wanrooy, Dominick Schienstock, Yannick O Alexandre, Oliver P Skinner, Rainon Joseph, Lynette Beattie, Scott N Mueller, Fei Chen, Ashraful Haque
{"title":"Plasmodium infection induces phenotypic, clonal, and spatial diversity among differentiating CD4<sup>+</sup> T cells.","authors":"Cameron G Williams, Marcela L Moreira, Takahiro Asatsuma, Hyun Jae Lee, Shihan Li, Thomas N Burn, Irving Barrera, Evan Murray, Megan S F Soon, Jessica A Engel, David S Khoury, Shirley Le, Brooke J Wanrooy, Dominick Schienstock, Yannick O Alexandre, Oliver P Skinner, Rainon Joseph, Lynette Beattie, Scott N Mueller, Fei Chen, Ashraful Haque","doi":"10.1016/j.celrep.2024.114754","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114754","url":null,"abstract":"","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Understanding molecular mechanisms of plant cellular response to heat stress will help to improve crop tolerance and yield in the global warming era. Here, we show that deacetylation of non-histone proteins mediated by cytoplasmic histone deacetylase HDA714 is required for plant tolerance to heat stress in rice. Heat stress reduces overall protein lysine acetylation, which depends on HDA714. Being induced by heat stress, HDA714 loss of function reduces, but its overexpression enhances rice tolerance to heat stress. Under heat stress, HDA714-mediated deacetylation of metabolic enzymes stimulates glycolysis. In addition, HDA714 protein is found within heat-induced stress granules (SGs), and many SG proteins are acetylated under normal temperature. HDA714 interacts with and deacetylates several SG proteins. HDA714 loss of function increases SG protein acetylation levels and impairs SG formation. Collectively, these results indicate that HDA714 responds to heat stress to deacetylate cellular proteins, control metabolic activities, stimulate SG formation, and confer heat tolerance in rice.
{"title":"A histone deacetylase confers plant tolerance to heat stress by controlling protein lysine deacetylation and stress granule formation in rice.","authors":"Zhengting Chen, Qiutao Xu, Jing Wang, Hebo Zhao, Yaping Yue, Biao Liu, Lizhong Xiong, Yu Zhao, Dao-Xiu Zhou","doi":"10.1016/j.celrep.2024.114642","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114642","url":null,"abstract":"<p><p>Understanding molecular mechanisms of plant cellular response to heat stress will help to improve crop tolerance and yield in the global warming era. Here, we show that deacetylation of non-histone proteins mediated by cytoplasmic histone deacetylase HDA714 is required for plant tolerance to heat stress in rice. Heat stress reduces overall protein lysine acetylation, which depends on HDA714. Being induced by heat stress, HDA714 loss of function reduces, but its overexpression enhances rice tolerance to heat stress. Under heat stress, HDA714-mediated deacetylation of metabolic enzymes stimulates glycolysis. In addition, HDA714 protein is found within heat-induced stress granules (SGs), and many SG proteins are acetylated under normal temperature. HDA714 interacts with and deacetylates several SG proteins. HDA714 loss of function increases SG protein acetylation levels and impairs SG formation. Collectively, these results indicate that HDA714 responds to heat stress to deacetylate cellular proteins, control metabolic activities, stimulate SG formation, and confer heat tolerance in rice.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1016/j.celrep.2024.114656
Marina Vitoria Gomes, Pauline Landwerlin, Marie-Laure Diebold-Durand, Tajith B Shaik, Alexandre Durand, Edouard Troesch, Chantal Weber, Karl Brillet, Marianne Victoria Lemée, Christophe Decroos, Ludivine Dulac, Pierre Antony, Erwan Watrin, Eric Ennifar, Christelle Golzio, Christophe Romier
Cohesin is key to eukaryotic genome organization and acts throughout the cell cycle in an ATP-dependent manner. The mechanisms underlying cohesin ATPase activity are poorly understood. Here, we characterize distinct steps of the human cohesin ATPase cycle and show that the SMC1A and SMC3 ATPase domains undergo specific but concerted structural rearrangements along this cycle. Specifically, whereas the proximal coiled coil of the SMC1A ATPase domain remains conformationally stable, that of the SMC3 displays an intrinsic flexibility. The ATP-dependent formation of the heterodimeric SMC1A/SMC3 ATPase module (engaged state) favors this flexibility, which is counteracted by NIPBL and DNA binding (clamped state). Opening of the SMC3/RAD21 interface (open-engaged state) stiffens the SMC3 proximal coiled coil, thus constricting together with that of SMC1A the ATPase module DNA-binding chamber. The plasticity of the ATP-dependent interface between the SMC1A and SMC3 ATPase domains enables these structural rearrangements while keeping the ATP gate shut. VIDEO ABSTRACT.
凝聚素是真核生物基因组组织的关键,它以 ATP 依赖性方式作用于整个细胞周期。人们对凝聚素 ATPase 活性的机制知之甚少。在这里,我们描述了人类凝聚素 ATPase 周期的不同步骤,并表明 SMC1A 和 SMC3 ATPase 结构域在这一周期中经历了特定但一致的结构重排。具体来说,SMC1A ATPase 结构域的近端线圈在构象上保持稳定,而 SMC3 ATPase 结构域则显示出内在的灵活性。依赖 ATP 形成的异源二聚体 SMC1A/SMC3 ATPase 模块(啮合状态)有利于这种灵活性,而 NIPBL 和 DNA 结合(钳夹状态)则抵消了这种灵活性。打开 SMC3/RAD21 接口(开放-啮合状态)会使 SMC3 近端线圈变硬,从而与 SMC1A 一起收缩 ATPase 模块的 DNA 结合室。SMC1A 和 SMC3 ATPase 结构域之间的 ATP 依赖性界面的可塑性使这些结构重排得以实现,同时保持 ATP 门关闭。视频摘要。
{"title":"The cohesin ATPase cycle is mediated by specific conformational dynamics and interface plasticity of SMC1A and SMC3 ATPase domains.","authors":"Marina Vitoria Gomes, Pauline Landwerlin, Marie-Laure Diebold-Durand, Tajith B Shaik, Alexandre Durand, Edouard Troesch, Chantal Weber, Karl Brillet, Marianne Victoria Lemée, Christophe Decroos, Ludivine Dulac, Pierre Antony, Erwan Watrin, Eric Ennifar, Christelle Golzio, Christophe Romier","doi":"10.1016/j.celrep.2024.114656","DOIUrl":"https://doi.org/10.1016/j.celrep.2024.114656","url":null,"abstract":"<p><p>Cohesin is key to eukaryotic genome organization and acts throughout the cell cycle in an ATP-dependent manner. The mechanisms underlying cohesin ATPase activity are poorly understood. Here, we characterize distinct steps of the human cohesin ATPase cycle and show that the SMC1A and SMC3 ATPase domains undergo specific but concerted structural rearrangements along this cycle. Specifically, whereas the proximal coiled coil of the SMC1A ATPase domain remains conformationally stable, that of the SMC3 displays an intrinsic flexibility. The ATP-dependent formation of the heterodimeric SMC1A/SMC3 ATPase module (engaged state) favors this flexibility, which is counteracted by NIPBL and DNA binding (clamped state). Opening of the SMC3/RAD21 interface (open-engaged state) stiffens the SMC3 proximal coiled coil, thus constricting together with that of SMC1A the ATPase module DNA-binding chamber. The plasticity of the ATP-dependent interface between the SMC1A and SMC3 ATPase domains enables these structural rearrangements while keeping the ATP gate shut. VIDEO ABSTRACT.</p>","PeriodicalId":9798,"journal":{"name":"Cell reports","volume":null,"pages":null},"PeriodicalIF":7.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}