Molecules and Cells最新文献

Lipid dysregulation in polyglutamine diseases. 脂质失调在多谷氨酰胺疾病中的作用。

IF 8.2 3区生物学

Molecules and Cells Pub Date : 2026-10-14 DOI: 10.1016/j.mocell.2026.100406

Luhan Ni, Vaishnavi Veeranki, Byron Huang, Janghoo Lim

引用次数: 0

Ribosome-associated chaperone DNAJC2 titrates translation flux to alleviate the burden of co-translational quality control. 核糖体相关伴侣DNAJC2滴定翻译通量，减轻共翻译质量控制的负担。

IF 8.2 3区生物学

Molecules and Cells Pub Date : 2026-10-14 DOI: 10.1016/j.mocell.2026.100407

Jongmin Park, Youngim Yu, Heeju Park, Hyunwoo Bang, Jongbin Lee, Chunghun Lim

{"title":"Ribosome-associated chaperone DNAJC2 titrates translation flux to alleviate the burden of co-translational quality control.","authors":"Jongmin Park, Youngim Yu, Heeju Park, Hyunwoo Bang, Jongbin Lee, Chunghun Lim","doi":"10.1016/j.mocell.2026.100407","DOIUrl":"https://doi.org/10.1016/j.mocell.2026.100407","url":null,"abstract":"<p><p>Ribosome collisions during aberrant translation activate ribosome-associated quality control (RQC) to resolve stalled ribosome complexes and triage incomplete nascent chains. How this co-translational surveillance is coordinated with other ribosome-associated activities remains unclear. Here, we identify the ribosome-associated Hsp40 chaperone DNAJC2 that restrains translational flux and limits RQC engagement during collision-prone translation. Genetic epistasis analysis revealed that DNAJC2 titrates the flux of aberrant translation intermediates through the canonical RQC pathway, from the collision-sensing RQC factor ZNF598 to the downstream NEMF-LTN1 E3 ligase complex for proteasomal degradation. DNAJC2 depletion further sensitized cells to collision-induced ribotoxic stress response (RSR), indicating increased vulnerability to global translation stress. Mechanistically, loss of DNAJC2 accelerated translation elongation, thereby promoting ribosome collisions and ZNF598-dependent ribosome disassembly. Accordingly, reducing translational flux with the translation inhibitor homoharringtonine or a huntingtin upstream ORF rescued DNAJC2-depletion phenotypes during RQC-sensitive poly(A)-mediated translational stalling. Together, we propose that DNAJC2 acts as a translational rheostat to buffer ribosome collisions, prevent RQC overload, and set the threshold for RSR activation.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100407"},"PeriodicalIF":8.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Divergent proteomic landscapes and functional requirements for telomere maintenance in type I and type II ALT mESCs. I型和II型ALT mESCs端粒维持的不同蛋白质组学景观和功能需求。

IF 8.2 3区生物学

Molecules and Cells Pub Date : 2026-10-08 DOI: 10.1016/j.mocell.2026.100405

Hyunji Lee, Kyumin Park, Sandrine Sauzet, Subin Choi, Seung Woo Cho, Christine Hyein Chung, Sanghyun Sung, Dongan Kwon, Hobum Song, Serge Urbach, Hiroyuki Niida, Jérôme Déjardin, Junho Lee

{"title":"Divergent proteomic landscapes and functional requirements for telomere maintenance in type I and type II ALT mESCs.","authors":"Hyunji Lee, Kyumin Park, Sandrine Sauzet, Subin Choi, Seung Woo Cho, Christine Hyein Chung, Sanghyun Sung, Dongan Kwon, Hobum Song, Serge Urbach, Hiroyuki Niida, Jérôme Déjardin, Junho Lee","doi":"10.1016/j.mocell.2026.100405","DOIUrl":"https://doi.org/10.1016/j.mocell.2026.100405","url":null,"abstract":"<p><p>Alternative lengthening of telomeres (ALT) is a telomerase-independent, recombination-based pathway utilized by some cancers. Previously, we established two distinct types of ALT survivors derived from mouse embryonic stem cells (mESCs), characterized by either a unique non-telomeric insertion (type I) or canonical telomeric repeats (type II). In this study, we used telomere-specific proteomics to elucidate the divergent telomere maintenance strategies of these ALT types. We identified distinct proteomic profiles enriched in type I versus type II ALT telomeres. ICE1 is a component of the Little Elongation Complex, which is specifically recruited to type I ALT telomeres, where it supports the transcription of telomeric repeat-containing RNA (TERRA) and telomere maintenance. In contrast, the serine/threonine kinase VRK2 is highly enriched in type II ALT telomeres, where it regulates telomere-nuclear envelope interactions. Depletion of ICE1 or VRK2 impairs telomere stability in type I and type II ALT mESCs, respectively. Our results indicate that cells with a common mESC origin can adopt distinct molecular mechanisms to maintain telomere integrity, highlighting the mechanistic heterogeneity of ALT telomere maintenance.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100405"},"PeriodicalIF":8.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Pre-splicing factors associate with UpA-rich RNA and limit flavivirus replication. 剪接前因子与富含upa的RNA相关，限制黄病毒复制。

IF 8.2 3区生物学

Molecules and Cells Pub Date : 2026-10-05 DOI: 10.1016/j.mocell.2026.100404

Joyce W M van Bree, Kristel Doets, Carmen van de Waterbeemd, Sjef Boeren, Monique M van Oers, Gorben P Pijlman, Jelke J Fros

{"title":"Pre-splicing factors associate with UpA-rich RNA and limit flavivirus replication.","authors":"Joyce W M van Bree, Kristel Doets, Carmen van de Waterbeemd, Sjef Boeren, Monique M van Oers, Gorben P Pijlman, Jelke J Fros","doi":"10.1016/j.mocell.2026.100404","DOIUrl":"https://doi.org/10.1016/j.mocell.2026.100404","url":null,"abstract":"<p><p>The RNA of all living organisms and most viruses exhibits pervasive suppression of uracil-adenine (UpA) dinucleotides, yet the underlying molecular mechanisms remain poorly understood. Here, we use RNA affinity purification coupled with mass spectrometry to identify diverse host factors that preferentially bind UpA-high RNA sequences. The identified proteins include the canonical antiviral proteins IFIT1 and OAS1, as well as multiple components of the U1 and U2 small nuclear ribonucleoproteins (snRNPs), core elements of the splicing machinery. These splicing factors display increased affinity for artificially UpA-enriched RNA and the West Nile virus (WNV) 3' UTR, which naturally contains higher frequencies of UpA dinucleotides. The functional relevance of splicing factor interactions was demonstrated by pharmacological inhibition of early splicing events, which partially restored the replicative fitness of synonymously recoded and otherwise attenuated UpA-high mutants of Zika virus and WNV. Together, these findings reveal a novel antiviral role for splicing factors, linking their preferential association with UpA-rich RNA to the restriction of UpA-high viruses. Given the evolutionary conservation of the splicing machinery, our results suggest that splicing factor-mediated recognition may contribute to maintain the universal suppression of UpA dinucleotides in host and viral RNA.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100404"},"PeriodicalIF":8.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

From Retina to Brain: Viral Tools for Targeting Retinal Cells and Mapping Visual Circuits. 从视网膜到大脑：瞄准视网膜细胞和绘制视觉回路的病毒工具。

IF 8.2 3区生物学

Molecules and Cells Pub Date : 2026-09-30 DOI: 10.1016/j.mocell.2026.100403

Venu Talla, Kevin K Park

{"title":"From Retina to Brain: Viral Tools for Targeting Retinal Cells and Mapping Visual Circuits.","authors":"Venu Talla, Kevin K Park","doi":"10.1016/j.mocell.2026.100403","DOIUrl":"https://doi.org/10.1016/j.mocell.2026.100403","url":null,"abstract":"<p><p>The retina serves as a uniquely accessible entry point to the central nervous system, enabling both cell type-specific manipulation and circuit-level interrogation of visual pathways. Viral vectors have emerged as indispensable tools in this context, facilitating precise gene delivery, functional perturbation, and connectivity mapping across retinal and brain circuits. Among retinal neurons, retinal ganglion cells (RGCs) represent a major focus due to their role as the sole output neurons conveying visual information to central targets. Accordingly, recent advances in viral engineering including capsid design, transcriptional targeting, and synthetic regulatory elements have significantly improved the efficiency and specificity of RGC-directed gene delivery, while also enabling targeting of diverse retinal cell populations. Beyond retinal targeting, viral tools have transformed the study of RGC connectivity with downstream brain nuclei. In particular, transsynaptic and projection-specific viral strategies now enable mapping of RGC inputs and outputs across visual pathways with increasing precision. Approaches using retrograde AAVs, monosynaptic rabies systems, and anterograde tracers have revealed complex, cell type-dependent wiring patterns linking the retina to thalamic, midbrain, and cortical circuits. In this review, we highlight current viral technologies for targeting RGCs and other retinal cell types and subsequently discuss viral approaches for dissecting retinal-brain connectivity. Together, these complementary strategies provide a powerful framework for linking molecular identity, circuit architecture, and visual function, thereby advancing both basic neuroscience and translational efforts in vision research.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100403"},"PeriodicalIF":8.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Amygdala-hippocampus circuit regulates stress coping via mGluR5-dependent BDNF signaling 杏仁核-海马回路通过mglur5依赖性BDNF信号传导调节应激应对。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-03-01 Epub Date: 2026-01-21 DOI: 10.1016/j.mocell.2026.100320

Tae-Eun Kim , Tae-Yong Choi , Ja Wook Koo , Jeongseop Kim

{"title":"Amygdala-hippocampus circuit regulates stress coping via mGluR5-dependent BDNF signaling","authors":"Tae-Eun Kim , Tae-Yong Choi , Ja Wook Koo , Jeongseop Kim","doi":"10.1016/j.mocell.2026.100320","DOIUrl":"10.1016/j.mocell.2026.100320","url":null,"abstract":"<div><div>Stress-related psychiatric disorders are underpinned by dysfunction in the prefrontal cortex and hippocampus; however, the underlying circuit-specific mechanisms remain ill-defined. Here, we identified the basolateral amygdala (BLA)-to-ventral hippocampus (vHPC) circuit as a critical regulator of stress-coping behaviors. Although chronic social defeat stress reduced the mGluR5 expression in both the vHPC and medial prefrontal cortex (mPFC), our circuit-specific behavioral analysis revealed that the activation of the BLA-vHPC circuit produced a significantly greater improvement in coping behavior compared with the activation of the BLA-mPFC circuit. Subsequently, we mechanistically demonstrated that reduced mGluR5 in the vHPC directly impairs CREB-mediated brain-derived neurotrophic factor (BDNF) transcription, a molecular cascade tightly linked to passive coping. These findings reveal a novel circuit-specific molecular mechanism governing stress recovery, positioning the mGluR5-BDNF pathway as a highly specific and promising therapeutic target for future gene therapy interventions.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"49 3","pages":"Article 100320"},"PeriodicalIF":6.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Cover and caption 封面及标题

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-03-01 Epub Date: 2026-02-26 DOI: 10.1016/S1016-8478(26)00027-0

引用次数: 0

HAP1 interaction with KCNQ4 attenuates channel surface expression and function HAP1与KCNQ4的相互作用减弱了通道表面的表达和功能。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-03-01 Epub Date: 2026-01-29 DOI: 10.1016/j.mocell.2026.100322

Jung Ah Kim , Kyung Seok Oh , Jae Won Roh , Young Ik Koh , Haiyue Lin , Jinsei Jung , Heon Yung Gee

{"title":"HAP1 interaction with KCNQ4 attenuates channel surface expression and function","authors":"Jung Ah Kim , Kyung Seok Oh , Jae Won Roh , Young Ik Koh , Haiyue Lin , Jinsei Jung , Heon Yung Gee","doi":"10.1016/j.mocell.2026.100322","DOIUrl":"10.1016/j.mocell.2026.100322","url":null,"abstract":"<div><div>The voltage–gated channel subfamily Q member 4 (KCNQ4), a K+ channel, is one of the most frequently mutated genes in autosomal dominant nonsyndromic hearing loss. KCNQ4, which contains 6 transmembrane domains and a long cytoplasmic C-terminal tail, plays a crucial role in K+ recycling in the inner ear. Although KCNQ4 binds to various interactors, specific binding sites of the interactors remain elusive, and the biological significance of these interactions remains unknown. Therefore, this study aimed to discover a novel interactor of KCNQ4 and delineate its functional role in KCNQ4 regulation. We discovered a novel interactor of KCNQ4, huntingtin-associated protein 1 (HAP1), in addition to calmodulin, which interacts with the C-terminus of KCNQ4 using a yeast 2-hybrid assay. This interaction requires the B-segment of KCNQ4 as demonstrated by protein domain analysis. A thorough investigation of the biochemical and physiological consequences of this association revealed that HAP1 overexpression reduced surface expression and attenuated the potassium current mediated by KCNQ4. This suggests that HAP1 acts as a negative regulator of KCNQ4, potentially through the disruption of normal endocytic trafficking. These findings enhance the understanding of KCNQ4 regulation at the molecular level and highlight the potential of the HAP1-KCNQ4 axis as a target for interventions aimed at maintaining channel surface stability.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"49 3","pages":"Article 100322"},"PeriodicalIF":6.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Tankyrase-1-mediated PARsylation directs TFEB partner switching to regulate selective Wnt target gene expression tankyase -1介导的PARsylation指导TFEB伴侣转换以调节选择性Wnt靶基因的表达。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-03-01 Epub Date: 2026-01-08 DOI: 10.1016/j.mocell.2026.100313

Gahyeon Song , Chanhyeok Park , Eek-hoon Jho

{"title":"Tankyrase-1-mediated PARsylation directs TFEB partner switching to regulate selective Wnt target gene expression","authors":"Gahyeon Song , Chanhyeok Park , Eek-hoon Jho","doi":"10.1016/j.mocell.2026.100313","DOIUrl":"10.1016/j.mocell.2026.100313","url":null,"abstract":"<div><div>Wnt/β-catenin signaling coordinates developmental and oncogenic programs by modulating transcriptional networks. In addition to β-catenin, we previously identified transcription factor EB (TFEB)—a master regulator of lysosomal biogenesis and autophagy—as a Wnt-inducible co-regulator for a subset of Wnt target genes. However, the molecular mechanism underlying this selective transcriptional engagement remained unknown. Here, we show that Wnt3a stimulation promotes TFEB’s interaction with TCF-1/LEF-1 without altering lysosomal or autophagy-related gene regulation. This Wnt-specific association requires TFEB’s basic helix-loop-helix and leucine zipper domains and coincides with a marked reduction in TFEB-TFEB interaction. Mechanistically, Wnt activation triggers Tankyrase-1-mediated PARsylation of TFEB at K237 and K274 within the basic helix-loop-helix domain, switching its binding preference from homodimers to TCF-1/LEF-1 complexes. PARsylation-deficient TFEB mutants fail to associate with TCF-1/LEF-1 and cannot induce Wnt-TFEB target gene expression. These findings uncover a PARsylation-dependent partner-switching mechanism that reprograms TFEB’s transcriptional output under Wnt signaling.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"49 3","pages":"Article 100313"},"PeriodicalIF":6.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Practical NicE-seq workflow for chromatin accessibility analysis in plants 植物染色质接近性分析的实用NicE-seq工作流程。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-03-01 Epub Date: 2026-01-06 DOI: 10.1016/j.mocell.2026.100312

Zein Eddin Bader , Nassem Albakri , Dae-Jin Yun , Young Hun Song , Junghoon Park

{"title":"Practical NicE-seq workflow for chromatin accessibility analysis in plants","authors":"Zein Eddin Bader , Nassem Albakri , Dae-Jin Yun , Young Hun Song , Junghoon Park","doi":"10.1016/j.mocell.2026.100312","DOIUrl":"10.1016/j.mocell.2026.100312","url":null,"abstract":"<div><div>Open chromatin profiling identifies regulatory DNA regions that are accessible to transcription factors and other proteins, offering insights into gene regulation. Although ATAC-seq is commonly used for mapping open chromatin, standard techniques such as DNase-seq and ATAC-seq have limitations, including the need for large cell numbers or fresh (unfixed) samples. NicE-seq offers an alternative approach by using nicking endonucleases combined with polymerase–mediated biotin labeling. Here, we present a detailed analysis framework for NicE-seq data in plants using <em>Arabidopsis thaliana</em> as our reference species, adapted from the nf-core/atacseq pipeline with specific modifications. We emphasize the analytical differences between NicE-seq and ATAC-seq, describe data processing workflows, and illustrate methods for peak calling, annotation, and integration with transcriptomic data. This computational resource aims to guide researchers in applying NicE-seq, providing a basis for selecting between NicE-seq and ATAC-seq in plant epigenomic research, especially when working with challenging samples such as archived tissues or small cell populations.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"49 3","pages":"Article 100312"},"PeriodicalIF":6.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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