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Transcriptomic balance and optimal growth are determined by cell size 转录组平衡和最佳生长取决于细胞大小
IF 16 1区 生物学
Molecular Cell Pub Date : 2024-07-30 DOI: 10.1016/j.molcel.2024.07.005
{"title":"Transcriptomic balance and optimal growth are determined by cell size","authors":"","doi":"10.1016/j.molcel.2024.07.005","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.07.005","url":null,"abstract":"<p>Cell size and growth are intimately related across the evolutionary scale, but whether cell size is important to attain maximal growth or fitness is still an open question. We show that growth rate is a non-monotonic function of cell volume, with maximal values around the critical size of wild-type yeast cells. The transcriptome of yeast and mouse cells undergoes a relative inversion in response to cell size, which we associate theoretically and experimentally with the necessary genome-wide diversity in RNA polymerase II affinity for promoters. Although highly expressed genes impose strong negative effects on fitness when the DNA/mass ratio is reduced, transcriptomic alterations mimicking the relative inversion by cell size strongly restrain cell growth. In all, our data indicate that cells set the critical size to obtain a properly balanced transcriptome and, as a result, maximize growth and fitness during proliferation.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794973","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
Polysome collapse and RNA condensation fluidize the cytoplasm 多聚体崩解和 RNA 凝聚使细胞质流动起来
IF 16 1区 生物学
Molecular Cell Pub Date : 2024-07-25 DOI: 10.1016/j.molcel.2024.06.024
{"title":"Polysome collapse and RNA condensation fluidize the cytoplasm","authors":"","doi":"10.1016/j.molcel.2024.06.024","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.024","url":null,"abstract":"<p>The cell interior is packed with macromolecules of mesoscale size, and this crowded milieu significantly influences cellular physiology. Cellular stress responses almost universally lead to inhibition of translation, resulting in polysome collapse and release of mRNA. The released mRNA molecules condense with RNA-binding proteins to form ribonucleoprotein (RNP) condensates known as processing bodies and stress granules. Here, we show that polysome collapse and condensation of RNA transiently fluidize the cytoplasm, and coarse-grained molecular dynamic simulations support this as a minimal mechanism for the observed biophysical changes. Increased mesoscale diffusivity correlates with the efficient formation of quality control bodies (Q-bodies), membraneless organelles that compartmentalize misfolded peptides during stress. Synthetic, light-induced RNA condensation also fluidizes the cytoplasm. Together, our study reveals a functional role for stress-induced translation inhibition and formation of RNP condensates in modulating the physical properties of the cytoplasm to enable efficient response of cells to stress conditions.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754326","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
At the end, it is POT1 again: Phosphorylation allows human telomeric protein POT1 to recruit the C-rich strand end replication machinery 最后，又是 POT1：磷酸化使人类端粒蛋白 POT1 能够招募富 C 链末端复制机器
IF 16 1区 生物学
Molecular Cell Pub Date : 2024-07-25 DOI: 10.1016/j.molcel.2024.06.030
{"title":"At the end, it is POT1 again: Phosphorylation allows human telomeric protein POT1 to recruit the C-rich strand end replication machinery","authors":"","doi":"10.1016/j.molcel.2024.06.030","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.030","url":null,"abstract":"<p>Recently in <em>Cell</em>, Cai et al.<span><span><sup>1</sup></span></span> reported how phosphorylation of human shelterin protein POT1 allows it to recruit the telomeric C-rich strand replication machinery, providing mechanistic insights into an understudied area of telomere biology with implications for telomere biology disorders.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754325","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
SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition SARS-CoV-2 Omicron XBB 系尖峰结构、构象、抗原性和受体识别
IF 16 1区 生物学
Molecular Cell Pub Date : 2024-07-25 DOI: 10.1016/j.molcel.2024.06.028
{"title":"SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition","authors":"","doi":"10.1016/j.molcel.2024.06.028","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.028","url":null,"abstract":"<p>A recombinant lineage of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, named XBB, appeared in late 2022 and evolved descendants that successively swept local and global populations. XBB lineage members were noted for their improved immune evasion and transmissibility. Here, we determine cryoelectron microscopy (cryo-EM) structures of XBB.1.5, XBB.1.16, EG.5, and EG.5.1 spike (S) ectodomains to reveal reinforced 3-receptor binding domain (RBD)-down receptor-inaccessible closed states mediated by interprotomer RBD interactions previously observed in BA.1 and BA.2. Improved XBB.1.5 and XBB.1.16 RBD stability compensated for stability loss caused by early Omicron mutations, while the F456L substitution reduced EG.5 RBD stability. S1 subunit mutations had long-range impacts on conformation and epitope presentation in the S2 subunit. Our results reveal continued S protein evolution via simultaneous optimization of multiple parameters, including stability, receptor binding, and immune evasion, and the dramatic effects of relatively few residue substitutions in altering the S protein conformational landscape.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754329","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
Splicing regulation of DNA repair via CCAR1 通过 CCAR1 对 DNA 修复进行剪接调控
IF 16 1区 生物学
Molecular Cell Pub Date : 2024-07-25 DOI: 10.1016/j.molcel.2024.06.012
{"title":"Splicing regulation of DNA repair via CCAR1","authors":"","doi":"10.1016/j.molcel.2024.06.012","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.012","url":null,"abstract":"In this issue of Molecular Cell, Harada et al.1 and Karasu et al.2 identify CCAR1 as a novel regulator of the Fanconi anemia/BRCA DNA repair pathway v…","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754324","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
STING: Stay near to STIM(1) neuroprotection STING：靠近 STIM(1) 神经保护装置
IF 16 1区 生物学
Molecular Cell Pub Date : 2024-07-25 DOI: 10.1016/j.molcel.2024.06.034
{"title":"STING: Stay near to STIM(1) neuroprotection","authors":"","doi":"10.1016/j.molcel.2024.06.034","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.034","url":null,"abstract":"<p>In a recent publication in <em>Cell</em>, Woo et al.<span><span><sup>1</sup></span></span> report that stimulator of interferon genes (STING) links inflammation with glutamate-driven excitotoxicity to induce ferroptosis, identifying a mechanism of inflammation-induced neurodegeneration and also a novel candidate therapeutic target for multiple sclerosis.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754434","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
Sweetening mitochondria: Hexokinase shields mitochondria from fission when glucose is low 使线粒体变甜当葡萄糖含量低时，Hexokinase 保护线粒体不发生分裂
IF 16 1区 生物学
Molecular Cell Pub Date : 2024-07-25 DOI: 10.1016/j.molcel.2024.06.035
{"title":"Sweetening mitochondria: Hexokinase shields mitochondria from fission when glucose is low","authors":"","doi":"10.1016/j.molcel.2024.06.035","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.035","url":null,"abstract":"<p>In this issue of <em>Molecular Cell</em>, Pilic et al.<span><span><sup>1</sup></span></span> show that hexokinase, the first enzyme of glycolysis, forms perimitochondrial rings that prevent mitochondrial fragmentation when ATP levels drop.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764491","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
Blending and separating dynamics of RNA-binding proteins develop architectural splicing networks spreading throughout the nucleus RNA 结合蛋白的混合和分离动态发展出遍布整个细胞核的结构剪接网络
IF 16 1区 生物学
Molecular Cell Pub Date : 2024-07-24 DOI: 10.1016/j.molcel.2024.07.001
{"title":"Blending and separating dynamics of RNA-binding proteins develop architectural splicing networks spreading throughout the nucleus","authors":"","doi":"10.1016/j.molcel.2024.07.001","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.07.001","url":null,"abstract":"<p>The eukaryotic nucleus has a highly organized structure. Although the spatiotemporal arrangement of spliceosomes on nascent RNA drives splicing, the nuclear architecture that directly supports this process remains unclear. Here, we show that RNA-binding proteins (RBPs) assembled on RNA form meshworks in human and mouse cells. Core and accessory RBPs in RNA splicing make two distinct meshworks adjacently but distinctly distributed throughout the nucleus. This is achieved by mutual exclusion dynamics between the charged and uncharged intrinsically disordered regions (IDRs) of RBPs. These two types of meshworks compete for spatial occupancy on pre-mRNA to regulate splicing. Furthermore, the optogenetic enhancement of the RBP meshwork causes aberrant splicing, particularly of genes involved in neurodegeneration. Genetic mutations associated with neurodegenerative diseases are often found in the IDRs of RBPs, and cells harboring these mutations exhibit impaired meshwork formation. Our results uncovered the spatial organization of RBP networks to drive RNA splicing.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754534","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
Mechanisms for HNH-mediated target DNA cleavage in type I CRISPR-Cas systems I 型 CRISPR-Cas 系统中 HNH 介导的目标 DNA 切割机制
IF 16 1区 生物学
Molecular Cell Pub Date : 2024-07-23 DOI: 10.1016/j.molcel.2024.06.033
{"title":"Mechanisms for HNH-mediated target DNA cleavage in type I CRISPR-Cas systems","authors":"","doi":"10.1016/j.molcel.2024.06.033","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.033","url":null,"abstract":"<p>The metagenome-derived type I-E and type I-F variant CRISPR-associated complex for antiviral defense (Cascade) complexes, fused with HNH domains, precisely cleave target DNA, representing recently identified genome editing tools. However, the underlying working mechanisms remain unknown. Here, structures of type I-F<sup>HNH</sup> and I-E<sup>HNH</sup> Cascade complexes at different states are reported. In type I-F<sup>HNH</sup> Cascade, Cas8f<sup>HNH</sup> loosely attaches to Cascade head and is adjacent to the 5′ end of the target single-stranded DNA (ssDNA). Formation of the full R-loop drives the Cascade head to move outward, allowing Cas8f<sup>HNH</sup> to detach and rotate ∼150° to accommodate target ssDNA for cleavage. In type I-E<sup>HNH</sup> Cascade, Cas5e<sup>HNH</sup> domain is adjacent to the 5′ end of the target ssDNA. Full crRNA-target pairing drives the lift of the Cascade head, widening the substrate channel for target ssDNA entrance. Altogether, these analyses into both complexes revealed that crRNA-guided positioning of target DNA and target DNA-induced HNH unlocking are two key factors for their site-specific cleavage of target DNA.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754536","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
Technological advancements in deciphering RNA-RNA interactions 破译 RNA-RNA 相互作用的技术进步
IF 16 1区 生物学
Molecular Cell Pub Date : 2024-07-23 DOI: 10.1016/j.molcel.2024.06.036
{"title":"Technological advancements in deciphering RNA-RNA interactions","authors":"","doi":"10.1016/j.molcel.2024.06.036","DOIUrl":"https://doi.org/10.1016/j.molcel.2024.06.036","url":null,"abstract":"<p>RNA-RNA interactions (RRIs) can dictate RNA molecules to form intricate higher-order structures and bind their RNA substrates in diverse biological processes. To elucidate the function, binding specificity, and regulatory mechanisms of various RNA molecules, especially the vast repertoire of non-coding RNAs, advanced technologies and methods that globally map RRIs are extremely valuable. In the past decades, many state-of-the-art technologies have been developed for this purpose. This review focuses on those high-throughput technologies for the global mapping of RRIs. We summarize the key concepts and the pros and cons of different technologies. In addition, we highlight the novel biological insights uncovered by these RRI mapping methods and discuss the future challenges for appreciating the crucial roles of RRIs in gene regulation across bacteria, viruses, archaea, and mammals.</p>","PeriodicalId":18950,"journal":{"name":"Molecular Cell","volume":null,"pages":null},"PeriodicalIF":16.0,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754535","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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