Journal of Molecular Cell Biology最新文献_第4页

Regulation of m6Am RNA modification and its implications in human diseases. m6Am RNA修饰的调控及其对人类疾病的影响。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjae012

Hao Jin, Zhouyuanjing Shi, Tianhua Zhou, Shanshan Xie

{"title":"Regulation of m6Am RNA modification and its implications in human diseases.","authors":"Hao Jin, Zhouyuanjing Shi, Tianhua Zhou, Shanshan Xie","doi":"10.1093/jmcb/mjae012","DOIUrl":"10.1093/jmcb/mjae012","url":null,"abstract":"N 6,2'-O-dimethyladenosine (m6Am) is a prevalent modification frequently found at the 5' cap-adjacent adenosine of messenger RNAs (mRNAs) and small nuclear RNAs (snRNAs) and the internal adenosine of snRNAs. This dynamic and reversible modification is under the regulation of methyltransferases phosphorylated CTD interacting factor 1 and methyltransferase-like protein 4, along with the demethylase fat mass and obesity-associated protein. m6Am RNA modification plays a crucial role in the regulation of pre-mRNA splicing, mRNA stability, and translation, thereby influencing gene expression. In recent years, there has been growing interest in exploring the functions of m6Am and its relevance to human diseases. In this review, we provide a comprehensive overview of the current knowledge concerning m6Am, with a focus on m6Am-modifying enzymes, sequencing approaches for its detection, and its impacts on pre-mRNA splicing, mRNA stability, and translation regulation. Furthermore, we highlight the roles of m6Am in the context of obesity, viral infections, and cancers, unravelling its underlying regulatory mechanisms.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175129","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

Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair. 人类诱导多能干细胞中的端粒DNA断裂触发ATR介导的阻滞和端粒酶非依赖性的端粒损伤修复。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-26 DOI: 10.1093/jmcb/mjad058

Katrina N Estep, John W Tobias, Rafael J Fernandez, Brinley M Beveridge, F Brad Johnson

{"title":"Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair.","authors":"Katrina N Estep, John W Tobias, Rafael J Fernandez, Brinley M Beveridge, F Brad Johnson","doi":"10.1093/jmcb/mjad058","DOIUrl":"10.1093/jmcb/mjad058","url":null,"abstract":"Although mechanisms of telomere protection are well-defined in differentiated cells, how stem cells sense and respond to telomere dysfunction, in particular telomeric double-strand breaks (DSBs), is poorly characterized. Here, we report the DNA damage signaling, cell cycle, and transcriptome changes in human induced pluripotent stem cells (iPSCs) in response to telomere-internal DSBs. We engineer human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at telomeres. Using this model, we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DNA damage response, which leads to p53-independent cell cycle arrest in G2. Using CRISPR-Cas9 to cripple the catalytic domain of telomerase reverse transcriptase, we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres, which instead are effectively repaired by robust homologous recombination (HR). In contrast to HR-based telomere maintenance in mouse embryonic stem cells, where HR causes ZSCAN4-dependent extension of telomeres beyond their initial lengths, HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length, which is compatible with sustained survival of the cells over several days of TRF1-FokI induction. Our findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric DNA damage.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41099295","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 polarized multicomponent foundation upholds ciliary central microtubules. 纤毛中心微管由极化的多成分基础支撑。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-20 DOI: 10.1093/jmcb/mjae031

Qingxia Chen, Huijie Zhao, Xinwen Pan, Chuyu Fang, Benhua Qiu, Jingting Guo, Xiumin Yan, Xueliang Zhu

{"title":"A polarized multicomponent foundation upholds ciliary central microtubules.","authors":"Qingxia Chen, Huijie Zhao, Xinwen Pan, Chuyu Fang, Benhua Qiu, Jingting Guo, Xiumin Yan, Xueliang Zhu","doi":"10.1093/jmcb/mjae031","DOIUrl":"https://doi.org/10.1093/jmcb/mjae031","url":null,"abstract":"Cilia's back-and-forth beat pattern requires a central pair (CP) of microtubules. However, the mechanism by which the CP is upheld above the transition zone (TZ) remains unclear. Here, we showed that a rod-like substructure marked by Cep131 and ciliary Centrin serves as a polarized CP-supporting foundation. This CP-foundation (CPF) was assembled independently of the CP during ciliogenesis in mouse ependymal cells. It protruded from the distal end of the basal body out of the TZ to enwrap the proximal end of the CP. Through proximity labeling, we identified 26 potential CPF components, among which Ccdc148 specifically localized at the proximal region of Centrin-decorated CPF and was complementary to the Cep131-enriched distal region. Cep131 deficiency abolished the CPF, resulting in CP penetration into the TZ. Consequently, cilia became prone to ultrastructural abnormality and paralysis, and Cep131-deficient mice were susceptible to late-onset hydrocephalus. In addition to Centrin, phylogenetic analysis also indicated conservations of Ccdc131 and Ccdc148 from protists to mammals, suggesting that the CPF is an evolutionarily conserved multicomponent CP-supporting platform in cilia.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Modeling gastric intestinal metaplasia in 3D organoids using nitrosoguanidine. 利用亚硝基胍在三维有机体中模拟胃肠化生。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-17 DOI: 10.1093/jmcb/mjae030

Yuan Li, Jiena Chen, Tao Li, Jie Lin, Haocheng Zheng, Nadia Johnson, Xuebiao Yao, Xia Ding

{"title":"Modeling gastric intestinal metaplasia in 3D organoids using nitrosoguanidine.","authors":"Yuan Li, Jiena Chen, Tao Li, Jie Lin, Haocheng Zheng, Nadia Johnson, Xuebiao Yao, Xia Ding","doi":"10.1093/jmcb/mjae030","DOIUrl":"https://doi.org/10.1093/jmcb/mjae030","url":null,"abstract":"Gastric intestinal metaplasia (GIM) represents a precancerous stage characterized by morphological and pathophysiological changes in the gastric mucosa, where gastric epithelial cells transform into a phenotype resembling that of intestinal cells. Previous studies have demonstrated that the intragastric administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces both gastric carcinoma and intestinal metaplasia in mice. Here, we show that MNNG induces GIM in three-dimensional (3D) mouse organoids. Our histological analyses reveal that MNNG-induced gastric organoids undergo classical morphological alterations, exhibiting a distinct up-regulation of CDX2 and MUC2, along with a down-regulation of ATP4B and MUC6. Importantly, metaplastic cells observed in MNNG-treated organoids originate from MIST1+ cells, indicating their gastric chief cell lineage. Functional analyses show that activation of the RAS signaling pathway drives MNNG-induced metaplasia in 3D organoids, mirroring the characteristics observed in human GIM. Consequently, modeling intestinal metaplasia using 3D organoids offers valuable insights into the molecular mechanisms and spatiotemporal dynamics of the gastric epithelial lineage during the development of intestinal metaplasia within the gastric mucosa. We conclude that the MNNG-induced metaplasia model utilizing 3D organoids provides a robust platform for developing preventive and therapeutic strategies to mitigate the risk of gastric cancer before precancerous lesions occur.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Sterile activation of RNA-sensing pathways in autoimmunity. 无菌激活自身免疫中的 RNA 传感途径

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-08-14 DOI: 10.1093/jmcb/mjae029

Jiaxin Li, Junyan Zhu, Hui Yang, Fajian Hou

引用次数: 0

Dual role of PpV in Drosophila crystal cell proliferation and survival. PpV 在果蝇晶体细胞增殖和存活中的双重作用

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-31 DOI: 10.1093/jmcb/mjae028

Wang Luo, Fang Zhang, Fangzhen Zhao, Yang Fang, Long Zhao, Ying Su

{"title":"Dual role of PpV in Drosophila crystal cell proliferation and survival.","authors":"Wang Luo, Fang Zhang, Fangzhen Zhao, Yang Fang, Long Zhao, Ying Su","doi":"10.1093/jmcb/mjae028","DOIUrl":"https://doi.org/10.1093/jmcb/mjae028","url":null,"abstract":"Drosophila melanogaster crystal cells are a specialized type of blood cells for innate immune process upon injury. Under normal conditions, crystal cells rarely proliferate and constitute a small proportion of fly blood cells. Notch signaling has been known to guide the cell fate determination of crystal cells and maintain their survival. Here, we reported that protein phosphatase V (PpV), the unique catalytic subunit of protein phosphatase 6 in Drosophila, is a novel regulator of crystal cell proliferation and integrity. We found that PpV proteins highly accumulated in crystal cells in the larval hematopoietic organ termed the lymph gland. Silencing PpV using RNA interference led to increased crystal cell proliferation in a Notch-independent manner and induced crystal cell rupture dependent on Notch signaling. Moreover, additive PpV prevented the rupture of crystal cells in lymph glands upon a needle injury, suggesting the involvement of PpV in wound healing. Altogether, our results indicated that PpV plays a dual role in lymph glands, preventing crystal cell proliferation to limit the cell number, as well as inhibiting crystal cell rupture to maintain their survival.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Aurora B promotes the CENP-T-CENP-W interaction to guide accurate chromosome segregation in mitosis. 极光 B 促进 CENP-T-CENP-W 相互作用，引导有丝分裂中染色体的准确分离。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae001

Wei Liu, Zhen Dou, Chunyue Wang, Gangyin Zhao, Fengge Wu, Chunli Wang, Felix Aikhionbare, Mingliang Ye, Divine Mensah Sedzro, Zhenye Yang, Chuanhai Fu, Zhikai Wang, Xinjiao Gao, Xuebiao Yao, Xiaoyu Song, Xing Liu

{"title":"Aurora B promotes the CENP-T-CENP-W interaction to guide accurate chromosome segregation in mitosis.","authors":"Wei Liu, Zhen Dou, Chunyue Wang, Gangyin Zhao, Fengge Wu, Chunli Wang, Felix Aikhionbare, Mingliang Ye, Divine Mensah Sedzro, Zhenye Yang, Chuanhai Fu, Zhikai Wang, Xinjiao Gao, Xuebiao Yao, Xiaoyu Song, Xing Liu","doi":"10.1093/jmcb/mjae001","DOIUrl":"10.1093/jmcb/mjae001","url":null,"abstract":"Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules. Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network (CCAN) during chromosome segregation. CCAN contains 16 subunits, including CENP-W and CENP-T. However, the molecular recognition and mitotic regulation of the CCAN assembly remain elusive. Here, we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T. Aurora B phosphorylates CENP-W at threonine 60, which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis. These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417352","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

Antiviral factors and their counteraction by HIV-1: many uncovered and more to be discovered. 抗病毒因子及其对 HIV-1 的反作用：发现了许多，还有更多有待发现。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae005

Dorota Kmiec, Frank Kirchhoff

引用次数: 0

PLK1 phosphorylation of ZW10 guides accurate chromosome segregation in mitosis. ZW10的PLK1磷酸化可引导有丝分裂中染色体的准确分离。

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae008

Sm Faysal Bellah, Fangyuan Xiong, Zhen Dou, Fengrui Yang, Xing Liu, Xuebiao Yao, Xinjiao Gao, Liangyu Zhang

{"title":"PLK1 phosphorylation of ZW10 guides accurate chromosome segregation in mitosis.","authors":"Sm Faysal Bellah, Fangyuan Xiong, Zhen Dou, Fengrui Yang, Xing Liu, Xuebiao Yao, Xinjiao Gao, Liangyu Zhang","doi":"10.1093/jmcb/mjae008","DOIUrl":"10.1093/jmcb/mjae008","url":null,"abstract":"Stable transmission of genetic information during cell division requires faithful chromosome segregation. Mounting evidence has demonstrated that polo-like kinase 1 (PLK1) dynamics at kinetochores control correct kinetochore-microtubule attachments and subsequent silencing of the spindle assembly checkpoint. However, the mechanisms underlying PLK1-mediated silencing of the spindle checkpoint remain elusive. Here, we identified a regulatory mechanism by which PLK1-elicited zeste white 10 (ZW10) phosphorylation regulates spindle checkpoint silencing in mitosis. ZW10 is a cognate substrate of PLK1, and the phosphorylation of ZW10 at Ser12 enables dynamic ZW10-Zwint1 interactions. Inhibition of ZW10 phosphorylation resulted in misaligned chromosomes, while persistent expression of phospho-mimicking ZW10 mutant caused premature anaphase, in which sister chromatids entangled as cells entered anaphase. These findings reveal the previously uncharacterized PLK1-ZW10 interaction through which dynamic phosphorylation of ZW10 fine-tunes accurate chromosome segregation in mitosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11328731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944219","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

Organization of microtubule plus-end dynamics by phase separation in mitosis. 通过有丝分裂中的相分离组织微管加端动力学

IF 5.3 2区生物学

Journal of Molecular Cell Biology Pub Date : 2024-07-29 DOI: 10.1093/jmcb/mjae006

Fengrui Yang, Mingrui Ding, Xiaoyu Song, Fang Chen, Tongtong Yang, Chunyue Wang, Chengcheng Hu, Qing Hu, Yihan Yao, Shihao Du, Phil Y Yao, Peng Xia, Gregory Adams, Chuanhai Fu, Shengqi Xiang, Dan Liu, Zhikai Wang, Kai Yuan, Xing Liu

{"title":"Organization of microtubule plus-end dynamics by phase separation in mitosis.","authors":"Fengrui Yang, Mingrui Ding, Xiaoyu Song, Fang Chen, Tongtong Yang, Chunyue Wang, Chengcheng Hu, Qing Hu, Yihan Yao, Shihao Du, Phil Y Yao, Peng Xia, Gregory Adams, Chuanhai Fu, Shengqi Xiang, Dan Liu, Zhikai Wang, Kai Yuan, Xing Liu","doi":"10.1093/jmcb/mjae006","DOIUrl":"10.1093/jmcb/mjae006","url":null,"abstract":"In eukaryotes, microtubule polymers are essential for cellular plasticity and fate decisions. End-binding (EB) proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dynamics and chromosome segregation in mitosis. Here, we show that EB1 forms molecular condensates with TIP150 and MCAK through liquid-liquid phase separation to compartmentalize the kinetochore-microtubule plus-end machinery, ensuring accurate kinetochore-microtubule interactions during chromosome segregation in mitosis. Perturbation of EB1-TIP150 polymer formation by a competing peptide prevents phase separation of the EB1-mediated complex and chromosome alignment at the metaphase equator in both cultured cells and Drosophila embryos. Lys220 of EB1 is dynamically acetylated by p300/CBP-associated factor in early mitosis, and persistent acetylation at Lys220 attenuates phase separation of the EB1-mediated complex, dissolves droplets in vitro, and harnesses accurate chromosome segregation. Our data suggest a novel framework for understanding the organization and regulation of eukaryotic spindle for accurate chromosome segregation in mitosis.","PeriodicalId":16433,"journal":{"name":"Journal of Molecular Cell Biology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697731","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