Journal of Molecular Cell Biology最新文献_第8页

SV2B defines a subpopulation of synaptic vesicles. SV2B 定义了突触小泡的一个亚群。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-04 DOI: 10.1093/jmcb/mjad054

Isabelle Paulussen, Hannes Beckert, Timothy F Musial, Lena J Gschossmann, Julia Wolf, Mathieu Schmitt, Jérôme Clasadonte, Georges Mairet-Coello, Christian Wolff, Susanne Schoch, Dirk Dietrich

{"title":"SV2B defines a subpopulation of synaptic vesicles.","authors":"Isabelle Paulussen, Hannes Beckert, Timothy F Musial, Lena J Gschossmann, Julia Wolf, Mathieu Schmitt, Jérôme Clasadonte, Georges Mairet-Coello, Christian Wolff, Susanne Schoch, Dirk Dietrich","doi":"10.1093/jmcb/mjad054","DOIUrl":"10.1093/jmcb/mjad054","url":null,"abstract":"Synaptic vesicles can undergo several modes of exocytosis, endocytosis, and trafficking within individual synapses, and their fates may be linked to different vesicular protein compositions. Here, we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron microscopy. SV2B was almost completely absent from docked vesicles and a distinct cluster of vesicles found near the active zone. In contrast, SV2A was found in all domains of the synapse and was slightly enriched near the active zone. SV2B and SV2A were found on the membrane in the peri-active zone, suggesting the recycling from both clusters of vesicles. SV2B knockout mice displayed an increased seizure induction threshold only in a model employing high-frequency stimulation. Our data show that glutamatergic synapses generate molecularly distinct populations of synaptic vesicles and are able to maintain them at steep spatial gradients. The almost complete absence of SV2B from vesicles at the active zone of wildtype mice may explain why SV2A has been found more important for vesicle release.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11184983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10173950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A computational study for understanding the impact of p120-catenin on the cis-dimerization of cadherin. 了解p120连环蛋白对钙粘蛋白顺式二聚作用影响的计算研究。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-04 DOI: 10.1093/jmcb/mjad055

Zhaoqian Su, Vinh H Vu, Deborah E Leckband, Yinghao Wu

{"title":"A computational study for understanding the impact of p120-catenin on the cis-dimerization of cadherin.","authors":"Zhaoqian Su, Vinh H Vu, Deborah E Leckband, Yinghao Wu","doi":"10.1093/jmcb/mjad055","DOIUrl":"10.1093/jmcb/mjad055","url":null,"abstract":"A prototype of cross-membrane signal transduction is that extracellular binding of cell surface receptors to their ligands induces intracellular signalling cascades. However, much less is known about the process in the opposite direction, called inside-out signalling. Recent studies show that it plays a more important role in regulating the functions of many cell surface receptors than we used to think. In particular, in cadherin-mediated cell adhesion, recent experiments indicate that intracellular binding of the scaffold protein p120-catenin (p120ctn) can promote extracellular clustering of cadherin and alter its adhesive function. The underlying mechanism, however, is not well understood. To explore possible mechanisms, we designed a new multiscale simulation procedure. Using all-atom molecular dynamics simulations, we found that the conformational dynamics of the cadherin extracellular region can be altered by the intracellular binding of p120ctn. More intriguingly, by integrating all-atom simulation results into coarse-grained random sampling, we showed that the altered conformational dynamics of cadherin caused by the binding of p120ctn can increase the probability of lateral interactions between cadherins on the cell surface. These results suggest that p120ctn could allosterically regulate the cis-dimerization of cadherin through two mechanisms. First, p120ctn controls the extracellular conformational dynamics of cadherin. Second, p120ctn oligomerization can further promote cadherin clustering. Therefore, our study provides a mechanistic foundation for the inside-out signalling in cadherin-mediated cell adhesion, while the computational framework can be generally applied to other cross-membrane signal transduction systems.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11121193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41179154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Loss of the vitamin D receptor triggers senescence in chronic myeloid leukemia via DDIT4-mediated DNA damage. 维生素D受体的缺失通过DDIT4介导的DNA损伤触发慢性粒细胞白血病的衰老。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-04 DOI: 10.1093/jmcb/mjad066

Yan Xu, Wentao Qi, Chengzu Zheng, Yuan Li, Zhiyuan Lu, Jianmin Guan, Chunhua Lu, Baobing Zhao

{"title":"Loss of the vitamin D receptor triggers senescence in chronic myeloid leukemia via DDIT4-mediated DNA damage.","authors":"Yan Xu, Wentao Qi, Chengzu Zheng, Yuan Li, Zhiyuan Lu, Jianmin Guan, Chunhua Lu, Baobing Zhao","doi":"10.1093/jmcb/mjad066","DOIUrl":"10.1093/jmcb/mjad066","url":null,"abstract":"Chronic myeloid leukemia (CML) is a hematopoietic malignancy driven by the fusion gene BCR::ABL1. Drug resistance to tyrosine kinase inhibitors (TKIs), due to BCR::ABL1 mutations and residual leukemia stem cells (LSCs), remains a major challenge in CML treatment. Here, we revealed the requirement of the vitamin D receptor (VDR) in the progression of CML. VDR was upregulated by BCR::ABL1 and highly expressed in CML cells. Interestingly, VDR knockdown inhibited the proliferation of CML cells driven by both BCR::ABL1 and TKI-resistant BCR::ABL1 mutations. Mechanistically, VDR transcriptionally regulated DDIT4 expression; reduced DDIT4 levels upon VDR knockdown triggered DNA damage and senescence via p53 signaling activation in CML cells. Furthermore, VDR deficiency not only suppressed tumor burden and progression in primary CML mice but also reduced the self-renewal capacity of CML-LSCs. Together, our study demonstrated that targeting VDR is a promising strategy to overcome TKI resistance and eradicate LSCs in CML.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11190374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50161875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

CBX7 reprograms metabolic flux to protect against meningioma progression by modulating the USP44/c-MYC/LDHA axis. CBX7通过调节USP44/c-MYC/LDHA轴来重新编程代谢通量以防止脑膜瘤的进展。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-04 DOI: 10.1093/jmcb/mjad057

Haixia Cheng, Lingyang Hua, Hailiang Tang, Zhongyuan Bao, Xiupeng Xu, Hongguang Zhu, Shuyang Wang, Zeyidan Jiapaer, Roma Bhatia, Ian F Dunn, Jiaojiao Deng, Daijun Wang, Shuchen Sun, Shihai Luan, Jing Ji, Qing Xie, Xinyu Yang, Ji Lei, Guoping Li, Xianli Wang, Ye Gong

{"title":"CBX7 reprograms metabolic flux to protect against meningioma progression by modulating the USP44/c-MYC/LDHA axis.","authors":"Haixia Cheng, Lingyang Hua, Hailiang Tang, Zhongyuan Bao, Xiupeng Xu, Hongguang Zhu, Shuyang Wang, Zeyidan Jiapaer, Roma Bhatia, Ian F Dunn, Jiaojiao Deng, Daijun Wang, Shuchen Sun, Shihai Luan, Jing Ji, Qing Xie, Xinyu Yang, Ji Lei, Guoping Li, Xianli Wang, Ye Gong","doi":"10.1093/jmcb/mjad057","DOIUrl":"10.1093/jmcb/mjad057","url":null,"abstract":"Meningioma is one of the most common primary neoplasms in the central nervous system, but no specific molecularly targeted therapy has been approved for the clinical treatment of aggressive meningiomas. There is hence an urgent demand to decrypt the biological and molecular landscape of malignant meningioma. Here, through the in-silica prescreening and 10-year follow-up studies of 445 meningioma patients, we uncovered that CBX7 expression progressively decreases with malignancy grade and neoplasia stage in meningioma, and a high CBX7 expression level predicts a favorable prognosis in meningioma patients. CBX7 restoration significantly induces cell cycle arrest and inhibits meningioma cell proliferation. iTRAQ-based proteomics analysis indicated that CBX7 restoration triggers the metabolic shift from glycolysis to oxidative phosphorylation. The mechanistic study demonstrated that CBX7 promotes the proteasome-dependent degradation of c-MYC protein by transcriptionally inhibiting the expression of a c-MYC deubiquitinase, USP44, consequently attenuates c-MYC-mediated transactivation of LDHA transcripts, and further inhibits glycolysis and subsequent cell proliferation. More importantly, the functional role of CBX7 was further confirmed in subcutaneous and orthotopic meningioma xenograft mouse models and meningioma patients. Altogether, our results shed light on the critical role of CBX7 in meningioma malignancy progression and identify the CBX7/USP44/c-MYC/LDHA axis as a promising therapeutic target against meningioma progression.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41133139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm. 来自严重急性呼吸系统综合征冠状病毒2型的独特ORF8蛋白与人类树突状细胞结合，并诱导超炎症细胞因子风暴。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-04 DOI: 10.1093/jmcb/mjad062

Matthias Hamdorf, Thomas Imhof, Ben Bailey-Elkin, Janina Betz, Sebastian J Theobald, Alexander Simonis, Veronica Di Cristanziano, Lutz Gieselmann, Felix Dewald, Clara Lehmann, Max Augustin, Florian Klein, Miguel A Alejandre Alcazar, Robert Rongisch, Mario Fabri, Jan Rybniker, Heike Goebel, Jörg Stetefeld, Bent Brachvogel, Claus Cursiefen, Manuel Koch, Felix Bock

{"title":"The unique ORF8 protein from SARS-CoV-2 binds to human dendritic cells and induces a hyper-inflammatory cytokine storm.","authors":"Matthias Hamdorf, Thomas Imhof, Ben Bailey-Elkin, Janina Betz, Sebastian J Theobald, Alexander Simonis, Veronica Di Cristanziano, Lutz Gieselmann, Felix Dewald, Clara Lehmann, Max Augustin, Florian Klein, Miguel A Alejandre Alcazar, Robert Rongisch, Mario Fabri, Jan Rybniker, Heike Goebel, Jörg Stetefeld, Bent Brachvogel, Claus Cursiefen, Manuel Koch, Felix Bock","doi":"10.1093/jmcb/mjad062","DOIUrl":"10.1093/jmcb/mjad062","url":null,"abstract":"The novel coronavirus pandemic, first reported in December 2019, was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection leads to a strong immune response and activation of antigen-presenting cells, which can elicit acute respiratory distress syndrome (ARDS) characterized by the rapid onset of widespread inflammation, the so-called cytokine storm. In response to viral infections, monocytes are recruited into the lung and subsequently differentiate into dendritic cells (DCs). DCs are critical players in the development of acute lung inflammation that causes ARDS. Here, we focus on the interaction of a specific SARS-CoV-2 open reading frame protein, ORF8, with DCs. We show that ORF8 binds to DCs, causes pre-maturation of differentiating DCs, and induces the secretion of multiple proinflammatory cytokines by these cells. In addition, we identified DC-SIGN as a possible interaction partner of ORF8 on DCs. Blockade of ORF8 leads to reduced production of IL-1β, IL-6, IL-12p70, TNF-α, MCP-1 (also named CCL2), and IL-10 by DCs. Therefore, a neutralizing antibody blocking the ORF8-mediated cytokine and chemokine response could be an improved therapeutic strategy against SARS-CoV-2.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61563196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The critical role of BTRC in hepatic steatosis as an ATGL E3 ligase. BTRC作为ATGL E3连接酶在肝脂肪变性中的关键作用。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-04 DOI: 10.1093/jmcb/mjad064

Weiwei Qi, Zhenzhen Fang, Chuanghua Luo, Honghai Hong, Yanlan Long, Zhiyu Dai, Junxi Liu, Yongcheng Zeng, Ti Zhou, Yong Xia, Xia Yang, Guoquan Gao

{"title":"The critical role of BTRC in hepatic steatosis as an ATGL E3 ligase.","authors":"Weiwei Qi, Zhenzhen Fang, Chuanghua Luo, Honghai Hong, Yanlan Long, Zhiyu Dai, Junxi Liu, Yongcheng Zeng, Ti Zhou, Yong Xia, Xia Yang, Guoquan Gao","doi":"10.1093/jmcb/mjad064","DOIUrl":"10.1093/jmcb/mjad064","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, is one of the commonest causes of liver dysfunction. Adipose triglyceride lipase (ATGL) is closely related to lipid turnover and hepatic steatosis as the speed-limited triacylglycerol lipase in liver lipolysis. However, the expression and regulation of ATGL in NAFLD remain unclear. Herein, our results showed that ATGL protein levels were decreased in the liver tissues of high-fat diet (HFD)-fed mice, naturally obese mice, and cholangioma/hepatic carcinoma patients with hepatic steatosis, as well as in the oleic acid-induced hepatic steatosis cell model, while ATGL mRNA levels were not changed. ATGL protein was mainly degraded through the proteasome pathway in hepatocytes. Beta-transducin repeat containing (BTRC) was upregulated and negatively correlated with the decreased ATGL level in these hepatic steatosis models. Consequently, BTRC was identified as the E3 ligase for ATGL through predominant ubiquitination at the lysine 135 residue. Moreover, adenovirus-mediated knockdown of BTRC ameliorated steatosis in HFD-fed mouse livers and oleic acid-treated liver cells via upregulating the ATGL level. Taken together, BTRC plays a crucial role in hepatic steatosis as a new ATGL E3 ligase and may serve as a potential therapeutic target for treating NAFLD.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10993717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49690972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Targeting dysregulated splicing factors in cancer: lessons learned from RBM10 deficiency. 靶向癌症中失调剪接因子：从RBM10缺乏中吸取的经验教训。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-04-04 DOI: 10.1093/jmcb/mjad063

Yongbo Wang, Zefeng Wang

引用次数: 0

Mitochondrial transport of catalytic RNAs and targeting of the organellar transcriptome in human cells. 线粒体运输催化 RNA 和人体细胞内细胞器转录组的靶向。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-01-17 DOI: 10.1093/jmcb/mjad051

Paweł Głodowicz, Konrad Kuczyński, Romain Val, André Dietrich, Katarzyna Rolle

{"title":"Mitochondrial transport of catalytic RNAs and targeting of the organellar transcriptome in human cells.","authors":"Paweł Głodowicz, Konrad Kuczyński, Romain Val, André Dietrich, Katarzyna Rolle","doi":"10.1093/jmcb/mjad051","DOIUrl":"10.1093/jmcb/mjad051","url":null,"abstract":"Mutations in the small genome present in mitochondria often result in severe pathologies. Different genetic strategies have been explored, aiming to rescue such mutations. A number of these strategies were based on the capacity of human mitochondria to import RNAs from the cytosol and designed to repress the replication of the mutated genomes or to provide the organelles with wild-type versions of mutant transcripts. However, the mutant RNAs present in mitochondria turned out to be an obstacle to therapy and little attention has been devoted so far to their elimination. Here, we present the development of a strategy to knockdown mitochondrial RNAs in human cells using the transfer RNA-like structure of Brome mosaic virus or Tobacco mosaic virus as a shuttle to drive trans-cleaving ribozymes into the organelles in human cell lines. We obtained a specific knockdown of the targeted mitochondrial ATP6 mRNA, followed by a deep drop in ATP6 protein and a functional impairment of the oxidative phosphorylation chain. Our strategy provides a powerful approach to eliminate mutant organellar transcripts and to analyse the control and communication of the human organellar genetic system.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11148835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10018208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

ANGPTL3 negatively regulates IL-1β-induced NF-κB activation by inhibiting the IL1R1-associated signaling complex assembly. ANGPTL3 通过抑制 IL1R1 相关信号复合体的组装，对 IL-1β 诱导的 NF-κB 激活进行负向调节。

IF 5.5 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-01-17 DOI: 10.1093/jmcb/mjad053

Yu Zhang, Zi-Tong Zhang, Shi-Yuan Wan, Jing Yang, Yu-Juan Wei, Hui-Jing Chen, Wan-Zhu Zhou, Qiu-Yi Song, Shu-Xuan Niu, Ling Zheng, Kun Huang

{"title":"ANGPTL3 negatively regulates IL-1β-induced NF-κB activation by inhibiting the IL1R1-associated signaling complex assembly.","authors":"Yu Zhang, Zi-Tong Zhang, Shi-Yuan Wan, Jing Yang, Yu-Juan Wei, Hui-Jing Chen, Wan-Zhu Zhou, Qiu-Yi Song, Shu-Xuan Niu, Ling Zheng, Kun Huang","doi":"10.1093/jmcb/mjad053","DOIUrl":"10.1093/jmcb/mjad053","url":null,"abstract":"Interleukin-1β (IL-1β)-induced signaling is one of the most important pathways in regulating inflammation and immunity. The assembly of the receptor complex, consisting of the ligand IL-1β, the IL-1 receptor (IL-1R) type 1 (IL1R1), and the IL-1R accessory protein (IL1RAP), initiates this signaling. However, how the IL1R1-associated complex is regulated remains elusive. Angiopoietin like 3 (ANGPTL3), a key inhibitor of plasma triglyceride clearance, is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms. Currently, ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases. However, most studies have focused on the secreted form of ANGPTL3, while its intracellular role is still largely unknown. Here, we report that intracellular ANGPTL3 acts as a negative regulator of IL-1β-triggered signaling. Overexpression of ANGPTL3 inhibited IL-1β-induced NF-κB activation and the transcription of inflammatory genes in HepG2, THP1, and HEK293T cells, while knockdown or knockout of ANGPTL3 resulted in opposite effects. Mechanistically, ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain and disrupted the assembly of the IL1R1-associated complex. Taken together, our study reveals a novel role for ANGPTL3 in inflammation, whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10076021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Distinct roles of two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA polymerase II transcription elongation. 两种 SEC 支架蛋白 AFF1 和 AFF4 在调节 RNA 聚合酶 II 转录伸长过程中的不同作用。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-01-17 DOI: 10.1093/jmcb/mjad049

Zhuanzhuan Che, Xiaoxu Liu, Qian Dai, Ke Fang, Chenghao Guo, Junjie Yue, Haitong Fang, Peng Xie, Zhuojuan Luo, Chengqi Lin

{"title":"Distinct roles of two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA polymerase II transcription elongation.","authors":"Zhuanzhuan Che, Xiaoxu Liu, Qian Dai, Ke Fang, Chenghao Guo, Junjie Yue, Haitong Fang, Peng Xie, Zhuojuan Luo, Chengqi Lin","doi":"10.1093/jmcb/mjad049","DOIUrl":"10.1093/jmcb/mjad049","url":null,"abstract":"The super elongation complex (SEC) containing positive transcription elongation factor b plays a critical role in regulating transcription elongation. AFF1 and AFF4, two members of the AF4/FMR2 family, act as central scaffold proteins of SEC and are associated with various human diseases. However, their precise roles in transcriptional control remain unclear. Here, we investigate differences in the genomic distribution patterns of AFF1 and AFF4 around transcription start sites (TSSs). AFF1 mainly binds upstream of the TSS, while AFF4 is enriched downstream of the TSS. Notably, disruption of AFF4 results in slow elongation and early termination in a subset of AFF4-bound active genes, whereas AFF1 deletion leads to fast elongation and transcriptional readthrough in the same subset of genes. Additionally, AFF1 knockdown increases AFF4 levels at chromatin, and vice versa. In summary, these findings demonstrate that AFF1 and AFF4 function antagonistically to regulate RNA polymerase II transcription.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11113081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9922959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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