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Deciphering the molecular logic of WOX5 function in the root stem cell organizer. 解密WOX5在根干细胞组织器中功能的分子逻辑
IF 9.4 1区 生物学
EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1038/s44318-024-00302-2
Ning Zhang, Pamela Bitterli, Peter Oluoch, Marita Hermann, Ernst Aichinger, Edwin P Groot, Thomas Laux
{"title":"Deciphering the molecular logic of WOX5 function in the root stem cell organizer.","authors":"Ning Zhang, Pamela Bitterli, Peter Oluoch, Marita Hermann, Ernst Aichinger, Edwin P Groot, Thomas Laux","doi":"10.1038/s44318-024-00302-2","DOIUrl":"10.1038/s44318-024-00302-2","url":null,"abstract":"<p><p>Plant and animal stem cells receive signals from their surrounding cells to stay undifferentiated. In the Arabidopsis root, the quiescent center (QC) acts as a stem cell organizer, signaling to the neighboring stem cells. WOX5 is a central transcription factor regulating QC function. However, due to the scarcity of QC cells, WOX5 functions in the QC are largely unexplored at a genomic scale. Here, we unveil the transcriptional and epigenetic landscapes of the QC and the role of WOX5 within them. We find that WOX5 functions both as a transcriptional repressor and activator, affecting histone modifications and chromatin accessibility. Our data expand on known WOX5 functions, such as the regulation of differentiation, cell division, and auxin biosynthesis. We also uncover unexpected WOX5-regulated pathways involved in nitrate transport and the regulation of basal expression levels of genes associated with mature root tissues. These data suggest a role for QC cells as reserve stem cells and primed cells for prospective progenitor fates. Taken together, these findings offer insights into the role of WOX5 at the QC and provide a basis for further analyses to advance our understanding of the nature of plant stem cell organizers.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"281-303"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular condensation of the CO/NF-YB/NF-YC/FT complex gates floral transition in Arabidopsis. CO/NF-YB/NF-YC/FT复合体的分子凝结可控制拟南芥的花期转换。
IF 9.4 1区 生物学
EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-20 DOI: 10.1038/s44318-024-00293-0
Xiang Huang, Zhiming Ma, Danxia He, Xiao Han, Xu Liu, Qiong Dong, Cuirong Tan, Bin Yu, Tiedong Sun, Lars Nordenskiöld, Lanyuan Lu, Yansong Miao, Xingliang Hou
{"title":"Molecular condensation of the CO/NF-YB/NF-YC/FT complex gates floral transition in Arabidopsis.","authors":"Xiang Huang, Zhiming Ma, Danxia He, Xiao Han, Xu Liu, Qiong Dong, Cuirong Tan, Bin Yu, Tiedong Sun, Lars Nordenskiöld, Lanyuan Lu, Yansong Miao, Xingliang Hou","doi":"10.1038/s44318-024-00293-0","DOIUrl":"10.1038/s44318-024-00293-0","url":null,"abstract":"<p><p>The plant master photoperiodic regulator CONSTANS (CO) interacts with Nuclear Factor-Y subunits B2 (NF-YB2) and C9 (NF-YC9) and transcriptionally activates the florigen gene FLOWERING LOCUS T (FT), regulating floral transition. However, the molecular mechanism of the functional four-component complex assembly in the nucleus remains elusive. We report that co-phase separation of CO with NF-YB2/NF-YC9/FT precisely controls heterogeneous CO assembly and FT transcriptional activation. In response to light signals, CO proteins form functional percolation clusters from a diffuse distribution in a B-box-motif-dependent manner. Multivalent coassembly with NF-YC9 and NF-YB2 prevents inhibitory condensate formation and is necessary to maintain proper CO assembly and material properties. The intrinsically disordered region (IDR) of NF-YC9, containing a polyglutamine motif, fine-tunes the functional properties of CO/NF-YB/NF-YC condensates. Specific FT promoter recognition with polyelectrolyte partitioning also enables the fluidic functional properties of CO/NF-YB/NF-YC/FT condensates. Our findings offer novel insights into the tunable macromolecular condensation of the CO/NF-YB/NF-YC/FT complex in controlling flowering in the photoperiod control.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"225-250"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Flagellar rotation facilitates the transfer of a bacterial conjugative plasmid. 鞭毛旋转有利于细菌共轭质粒的转移。
IF 9.4 1区 生物学
EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1038/s44318-024-00320-0
Saurabh Bhattacharya, Michal Bejerano-Sagie, Miriam Ravins, Liat Zeroni, Prabhjot Kaur, Venkadesaperumal Gopu, Ilan Rosenshine, Sigal Ben-Yehuda
{"title":"Flagellar rotation facilitates the transfer of a bacterial conjugative plasmid.","authors":"Saurabh Bhattacharya, Michal Bejerano-Sagie, Miriam Ravins, Liat Zeroni, Prabhjot Kaur, Venkadesaperumal Gopu, Ilan Rosenshine, Sigal Ben-Yehuda","doi":"10.1038/s44318-024-00320-0","DOIUrl":"10.1038/s44318-024-00320-0","url":null,"abstract":"<p><p>Conjugation-mediated DNA delivery is the primary mode for antibiotic resistance spread in bacteria; yet, molecular mechanisms regulating the conjugation process remain largely unexplored. While conjugative plasmids typically require bacterial attachment to solid surfaces for facilitation of donor-to-recipient proximity, the pLS20 conjugative plasmid, prevalent among Gram-positive Bacillus spp., uniquely requires fluid environments to enhance its transfer. Here, we show that pLS20, carried by Bacillus subtilis, induces multicellular clustering, which can accommodate various species, hence offering a stable platform for DNA delivery in a liquid milieu. We further discovered that induction of pLS20 promoters, governing crucial conjugative genes, is dependent on the presence of donor cell flagella, the major bacterial motility organelle. Moreover, the pLS20 regulatory circuit is controlled by a mechanosensing signal transduction pathway responsive to flagella rotation, thus activating conjugation gene expression exclusively during the host motile phase. This flagella-conjugation coupling strategy may allow the dissemination of the plasmid to remote destinations, allowing infiltration into new niches.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"587-611"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Kinesin-like motor protein KIF23 maintains neural stem and progenitor cell pools in the developing cortex. 运动蛋白样运动蛋白KIF23维持发育中的皮层中的神经干和祖细胞池。
IF 9.4 1区 生物学
EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-12-04 DOI: 10.1038/s44318-024-00327-7
Sharmin Naher, Kenji Iemura, Satoshi Miyashita, Mikio Hoshino, Kozo Tanaka, Shinsuke Niwa, Jin-Wu Tsai, Takako Kikkawa, Noriko Osumi
{"title":"Kinesin-like motor protein KIF23 maintains neural stem and progenitor cell pools in the developing cortex.","authors":"Sharmin Naher, Kenji Iemura, Satoshi Miyashita, Mikio Hoshino, Kozo Tanaka, Shinsuke Niwa, Jin-Wu Tsai, Takako Kikkawa, Noriko Osumi","doi":"10.1038/s44318-024-00327-7","DOIUrl":"10.1038/s44318-024-00327-7","url":null,"abstract":"<p><p>Accurate mitotic division of neural stem and progenitor cells (NSPCs) is crucial for the coordinated generation of progenitors and mature neurons, which determines cortical size and structure. While mutations in the kinesin-like motor protein KIF23 gene have been recently linked to microcephaly in humans, the underlying mechanisms remain elusive. Here, we explore the pivotal role of KIF23 in embryonic cortical development. We characterize the dynamic expression of KIF23 in the cortical NSPCs of mice, ferrets, and humans during embryonic neurogenesis. Knockdown of Kif23 in mice results in precocious neurogenesis and neuronal apoptosis, attributed to an accelerated cell cycle exit, likely resulting from disrupted mitotic spindle orientation and impaired cytokinesis. Additionally, KIF23 depletion perturbs the apical surface structure of NSPCs by affecting the localization of apical junction proteins. We further demonstrate that the phenotypes induced by Kif23 knockdown are rescued by introducing wild-type human KIF23, but not by a microcephaly-associated variant. Our findings unveil a previously unexplored role of KIF23 in neural stem and progenitor cell maintenance via regulating spindle orientation and apical structure in addition to cytokinesis, shedding light on microcephaly pathogenesis.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"331-355"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cyclin-dependent kinase inhibitor p18 regulates lineage transitions of excitatory neurons, astrocytes, and interneurons in the mouse cortex. 细胞周期蛋白依赖性激酶抑制剂p18调控小鼠大脑皮层兴奋性神经元、星形胶质细胞和中间神经元的谱系转换
IF 9.4 1区 生物学
EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-12-12 DOI: 10.1038/s44318-024-00325-9
Wonyoung Lee, Byunghee Kang, Hyo-Min Kim, Tsuyoshi Ishida, Minkyung Shin, Misato Iwashita, Masahiro Nitta, Aki Shiraishi, Hiroshi Kiyonari, Koichiro Shimoya, Kazuto Masamoto, Tae-Young Roh, Yoichi Kosodo
{"title":"Cyclin-dependent kinase inhibitor p18 regulates lineage transitions of excitatory neurons, astrocytes, and interneurons in the mouse cortex.","authors":"Wonyoung Lee, Byunghee Kang, Hyo-Min Kim, Tsuyoshi Ishida, Minkyung Shin, Misato Iwashita, Masahiro Nitta, Aki Shiraishi, Hiroshi Kiyonari, Koichiro Shimoya, Kazuto Masamoto, Tae-Young Roh, Yoichi Kosodo","doi":"10.1038/s44318-024-00325-9","DOIUrl":"10.1038/s44318-024-00325-9","url":null,"abstract":"<p><p>Neural stem cells (NSCs) can give rise to both neurons and glia, but the regulatory mechanisms governing their differentiation transitions remain incompletely understood. Here, we address the role of cyclin-dependent kinase inhibitors (CDKIs) in the later stages of dorsal cortical development. We find that the CDKIs p18 and p27 are upregulated at the onset of astrocyte generation. Acute manipulation of p18 and p27 levels shows that CDKIs modulate lineage switching between upper-layer neurons and astrocytes at the transitional stage. We generate a conditional knock-in mouse model to induce p18 in NSCs. The transcriptomic deconvolution of microdissected tissue reveals that increased levels of p18 promote glial cell development and activate Delta-Notch signaling. Furthermore, we show that p18 upregulates the homeobox transcription factor Dlx2 to subsequently induce the differentiation of olfactory bulb interneurons while reducing the numbers of upper-layer neurons and astrocytes at the perinatal stage. Clonal analysis using transposon-based reporters reveals that the transition from the astrocyte to the interneuron lineage is potentiated by p18 at the single-cell level. In sum, our study reports a function of p18 in determining the developmental boundaries among different cellular lineages arising sequentially from NSCs in the dorsal cortex.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":"382-412"},"PeriodicalIF":9.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanical signaling through membrane tension induces somal translocation during neuronal migration. 在神经元迁移过程中,机械信号通过膜张力诱导染色体易位。
IF 9.4 1区 生物学
EMBO Journal Pub Date : 2024-12-20 DOI: 10.1038/s44318-024-00326-8
Takunori Minegishi, Honami Hasebe, Tomoya Aoyama, Keiji Naruse, Yasufumi Takahashi, Naoyuki Inagaki
{"title":"Mechanical signaling through membrane tension induces somal translocation during neuronal migration.","authors":"Takunori Minegishi, Honami Hasebe, Tomoya Aoyama, Keiji Naruse, Yasufumi Takahashi, Naoyuki Inagaki","doi":"10.1038/s44318-024-00326-8","DOIUrl":"https://doi.org/10.1038/s44318-024-00326-8","url":null,"abstract":"<p><p>Neurons migrate in a saltatory manner by repeating two distinct steps: extension of the leading process and translocation of the cell body. The former step is critical for determining the migratory route in response to extracellular guidance cues. In the latter step, neurons must generate robust forces that translocate the bulky soma against mechanical barriers of the surrounding three-dimensional environment. However, the link between the leading process extension and subsequent somal translocation remains unknown. By using the membrane tension sensor Flipper-TR and scanning ion conductance microscopy, we show that leading process extension increases plasma membrane tension. The tension elevation activated the mechanosensitive ion channel Tmem63b and triggered Ca<sup>2+</sup> influx, leading to actomyosin activation at the rear of the cell. Blockade of this signaling pathway disturbed somal translocation, thereby inhibiting neuronal migration in three-dimensional environments. These data suggest that mechanical signaling through plasma membrane tension and mechano-channels links the leading process extension to somal translocation, allowing rapid and saltatory neuronal migration.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873227","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}
引用次数: 0
RNA-binding proteins hnRNPM and ELAVL1 promote type-I interferon induction downstream of the nucleic acid sensors cGAS and RIG-I. rna结合蛋白hnRNPM和ELAVL1促进i型干扰素在核酸传感器cGAS和rig - 1下游的诱导。
IF 9.4 1区 生物学
EMBO Journal Pub Date : 2024-12-20 DOI: 10.1038/s44318-024-00331-x
Alexander Kirchhoff, Anna-Maria Herzner, Christian Urban, Antonio Piras, Robert Düster, Julia Mahlberg, Agathe Grünewald, Thais M Schlee-Guimarães, Katrin Ciupka, Petro Leka, Robert J Bootz, Christina Wallerath, Charlotte Hunkler, Ann Kristin de Regt, Beate M Kümmerer, Maria Hønholt Christensen, Florian I Schmidt, Min Ae Lee-Kirsch, Claudia Günther, Hiroki Kato, Eva Bartok, Gunther Hartmann, Matthias Geyer, Andreas Pichlmair, Martin Schlee
{"title":"RNA-binding proteins hnRNPM and ELAVL1 promote type-I interferon induction downstream of the nucleic acid sensors cGAS and RIG-I.","authors":"Alexander Kirchhoff, Anna-Maria Herzner, Christian Urban, Antonio Piras, Robert Düster, Julia Mahlberg, Agathe Grünewald, Thais M Schlee-Guimarães, Katrin Ciupka, Petro Leka, Robert J Bootz, Christina Wallerath, Charlotte Hunkler, Ann Kristin de Regt, Beate M Kümmerer, Maria Hønholt Christensen, Florian I Schmidt, Min Ae Lee-Kirsch, Claudia Günther, Hiroki Kato, Eva Bartok, Gunther Hartmann, Matthias Geyer, Andreas Pichlmair, Martin Schlee","doi":"10.1038/s44318-024-00331-x","DOIUrl":"https://doi.org/10.1038/s44318-024-00331-x","url":null,"abstract":"<p><p>The cytosolic nucleic acid sensors RIG-I and cGAS induce type-I interferon (IFN)-mediated immune responses to RNA and DNA viruses, respectively. So far no connection between the two cytosolic pathways upstream of IKK-like kinase activation has been investigated. Here, we identify heterogeneous nuclear ribonucleoprotein M (hnRNPM) as a positive regulator of IRF3 phosphorylation and type-I IFN induction downstream of both cGAS and RIG-I. Combining interactome analysis with genome editing, we further uncover the RNA-binding protein ELAV-like protein 1 (ELAVL1; also known as human antigen R, HuR) as an hnRNPM interactor. Depletion of hnRNPM or ELAVL1 impairs type-I IFN induction by herpes simplex virus 1 or Sendai virus. In addition, we show that hnRNPM and ELAVL1 interact with TANK-binding kinase 1, IκB kinase ε, IκB kinase β, and NF-κB p65. Our confocal microscopy experiments demonstrate cytosolic and perinuclear interactions between hnRNPM, ELAVL1, and TBK1. Furthermore, pharmacological inhibition of ELAVL1 strongly reduces cytokine release from type-I interferonopathy patient fibroblasts. The RNA-binding proteins hnRNPM and ELAVL1 are the first non-redundant regulators to bridge the cGAS/STING and RIG-I/MAVS pathways. Overall, our study characterizes the hnRNPM-ELAVL1 complex as a novel system promoting antiviral defense, pointing to a potential therapeutic target to reduce auto-inflammation in patients with type-I interferonopathies.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873199","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}
引用次数: 0
Molecular mechanism of condensin I activation by KIF4A. KIF4A活化凝缩素I的分子机制。
IF 9.4 1区 生物学
EMBO Journal Pub Date : 2024-12-17 DOI: 10.1038/s44318-024-00340-w
Erin E Cutts, Damla Tetiker, Eugene Kim, Luis Aragon
{"title":"Molecular mechanism of condensin I activation by KIF4A.","authors":"Erin E Cutts, Damla Tetiker, Eugene Kim, Luis Aragon","doi":"10.1038/s44318-024-00340-w","DOIUrl":"https://doi.org/10.1038/s44318-024-00340-w","url":null,"abstract":"<p><p>During mitosis, the condensin I and II complexes compact chromatin into chromosomes. Loss of the chromokinesin, KIF4A, results in reduced condensin I association with chromosomes, but the molecular mechanism behind this phenotype is unknown. In this study, we reveal that KIF4A binds directly to the human condensin I HAWK subunit, NCAPG, via a conserved disordered short linear motif (SLiM) located in its C-terminal tail. KIF4A competes for NCAPG binding to an overlapping site with SLiMs at the N-terminus of NCAPH and the C-terminus of NCAPD2, which mediate two auto-inhibitory interactions within condensin I. Consistently, the KIF4A SLiM peptide alone is sufficient to stimulate ATPase and DNA loop extrusion activities of condensin I. We identify similar SLiMs in the known yeast condensin interactors, Sgo1 and Lrs4, which bind yeast condensin subunit, Ycg1, the equivalent HAWK to NCAPG. Our findings, together with previous work on condensin II and cohesin, demonstrate that SLiM binding to the NCAPG-equivalent HAWK subunit is a conserved mechanism of regulation in SMC complexes.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847449","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}
引用次数: 0
A nuclear protein quality control system for elimination of nucleolus-related inclusions. 消除核仁相关内含物的核蛋白质量控制系统。
IF 9.4 1区 生物学
EMBO Journal Pub Date : 2024-12-17 DOI: 10.1038/s44318-024-00333-9
Lorène Brunello, Jolanta Polanowska, Léo Le Tareau, Chantal Maghames, Virginie Georget, Charlotte Guette, Karima Chaoui, Stéphanie Balor, Marie-Françoise O'Donohue, Marie-Pierre Bousquet, Pierre-Emmanuel Gleizes, Dimitris P Xirodimas
{"title":"A nuclear protein quality control system for elimination of nucleolus-related inclusions.","authors":"Lorène Brunello, Jolanta Polanowska, Léo Le Tareau, Chantal Maghames, Virginie Georget, Charlotte Guette, Karima Chaoui, Stéphanie Balor, Marie-Françoise O'Donohue, Marie-Pierre Bousquet, Pierre-Emmanuel Gleizes, Dimitris P Xirodimas","doi":"10.1038/s44318-024-00333-9","DOIUrl":"https://doi.org/10.1038/s44318-024-00333-9","url":null,"abstract":"<p><p>The identification of pathways that control elimination of protein inclusions is essential to understand the cellular response to proteotoxicity, particularly in the nuclear compartment, for which our knowledge is limited. We report that stress-induced nuclear inclusions related to the nucleolus are eliminated upon stress alleviation during the recovery period. This process is independent of autophagy/lysosome and CRM1-mediated nuclear export pathways, but strictly depends on the ubiquitin-activating E1 enzyme, UBA1, and on nuclear proteasomes that are recruited into the formed inclusions. UBA1 activity is essential only for the recovery process but dispensable for nuclear inclusion formation. Furthermore, the E3 ligase HUWE1 and HSP70 are components of the ubiquitin/chaperone systems that promote inclusion elimination. The recovery process also requires RNA Pol I-dependent production of the lncRNA IGS<sub>42</sub> during stress. IGS<sub>42</sub> localises within the formed inclusions and promotes their elimination by preserving the mobility of resident proteins. These findings reveal a protein quality control system that operates within the nucleus for the elimination of stress-induced nucleolus-related inclusions.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848317","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}
引用次数: 0
Molecular mechanism targeting condensin for chromosome condensation. 以凝集素为染色体凝聚靶标的分子机制
IF 9.4 1区 生物学
EMBO Journal Pub Date : 2024-12-17 DOI: 10.1038/s44318-024-00336-6
Menglu Wang, Daniel Robertson, Juan Zou, Christos Spanos, Juri Rappsilber, Adele L Marston
{"title":"Molecular mechanism targeting condensin for chromosome condensation.","authors":"Menglu Wang, Daniel Robertson, Juan Zou, Christos Spanos, Juri Rappsilber, Adele L Marston","doi":"10.1038/s44318-024-00336-6","DOIUrl":"https://doi.org/10.1038/s44318-024-00336-6","url":null,"abstract":"<p><p>Genomes are organised into DNA loops by the Structural Maintenance of Chromosomes (SMC) proteins. SMCs establish functional chromosomal sub-domains for DNA repair, gene expression and chromosome segregation, but how SMC activity is specifically targeted is unclear. Here, we define the molecular mechanism targeting the condensin SMC complex to specific chromosomal regions in budding yeast. A conserved pocket on the condensin HAWK subunit Ycg1 binds to chromosomal receptors carrying a related motif, CR1. In early mitosis, CR1 motifs in receptors Sgo1 and Lrs4 recruit condensin to pericentromeres and rDNA, to facilitate sister kinetochore biorientation and rDNA condensation, respectively. We additionally find that chromosome arm condensation begins as sister kinetochores come under tension, in a manner dependent on the Ycg1 pocket. We propose that multiple CR1-containing proteins recruit condensin to chromosomes and identify several additional candidates based on their sequence. Overall, we uncover the molecular mechanism that targets condensin to functionalise chromosomal domains to achieve accurate chromosome segregation during mitosis.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847853","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}
引用次数: 0
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