Molecular Cell最新文献

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Unbalanced chromatin binding of Polycomb complexes drives neurodevelopmental disorders 多梳复合体的不平衡染色质结合导致神经发育障碍

IF 16 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell

Pub Date : 2026-02-06 DOI: 10.1016/j.molcel.2026.01.023

Rodrigo L. Borges, Gretter González-Blanco, Harikumar Arigela, Yingyu Huang, Lucas D. Caeiro, Nikolai Fattakhov, Stefano Lepore, Liliana Garcia-Martinez, Matea Maurice, Pushti D. Mehta, Emily J. Park, Kailynn MacGillivray, Jevithen Nehru, Matthew Chau, Maria C. Robayo, Clemer Abad, Alicia Bilbao-Martinez, Fabiola Monteiro, Xi Luo, Song Tan, Daniel Bilbao, Simone Sidoli, Bruno Di Stefano, Katherina Walz, Arneet L. Saltzman, Ramiro E. Verdun, Ramin Shiekhattar, Lluis Morey

引用次数: 0

RBPscan: A quantitative in vivo tool for profiling RNA-binding protein interactions RBPscan：分析rna结合蛋白相互作用的定量体内工具

IF 16 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell

Pub Date : 2026-02-06 DOI: 10.1016/j.molcel.2026.01.003

Dmitry A. Kretov, Owen Sanborn, Thora McIsaac, Elaine Park, Imrat Imrat, Samuel Wu, Marianne Régis, Louis-Mathieu Harvey, Daniel Cifuentes

RNA-binding proteins (RBPs) are essential regulators of gene expression at the post-transcriptional level, yet obtaining quantitative insights into RBP-RNA interactions in vivo remains challenging. Here, we developed RBP specificity and contextual analysis via nucleotide editing (RBPscan), which integrates RNA editing with massively parallel reporter assays to profile RBP binding in vivo. In RBPscan, fusion of an RBP to the adenosine deaminase acting on RNA (ADAR) catalytic domain induces RNA editing of a recorder mRNA carrying the tested RBP-binding site, serving as a readout of the RBP-RNA interaction. We demonstrate the utility of RBPscan in zebrafish embryos, human cells, and yeast, showing that it quantifies binding strength, resolves dissociation constants, identifies binding motifs for various RBPs, and links binding affinities to their impact on mRNA stability. RBPscan also provides positional mapping of Pumilio-binding sites in the long non-coding RNA NORAD. With its simplicity, scalability, and cross-system compatibility, RBPscan is a versatile tool for investigating protein-RNA interactions and complements established methods for studying post-transcriptional regulatory networks.

rna结合蛋白（rbp）在转录后水平是基因表达的重要调控因子，然而获得体内RBP-RNA相互作用的定量见解仍然具有挑战性。在这里，我们通过核苷酸编辑（RBPscan）开发了RBP特异性和上下文分析，该方法将RNA编辑与大量平行报告基因分析相结合，以分析RBP在体内的结合情况。在RBPscan中，RBP与作用于RNA的腺苷脱氨酶（ADAR）催化结构域的融合诱导携带被测RBP结合位点的记录mRNA的RNA编辑，作为RBP-RNA相互作用的读数。我们展示了RBPscan在斑马鱼胚胎、人类细胞和酵母中的应用，表明它可以量化结合强度，分解解离常数，识别各种rbp的结合基元，并将结合亲和力与它们对mRNA稳定性的影响联系起来。RBPscan还提供了长链非编码RNA NORAD中pumilio结合位点的定位图谱。RBPscan具有简单性、可扩展性和跨系统兼容性，是研究蛋白质- rna相互作用的通用工具，并补充了研究转录后调控网络的既定方法。

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引用次数: 0

Density transitions in the regulation of transcription 转录调控中的密度转变

IF 16 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell

Pub Date : 2026-02-06 DOI: 10.1016/j.molcel.2026.01.009

Ambuja Navalkar, Mikayla Eppert, Benjamin R. Sabari, Tanja Mittag

引用次数: 0

Asparagine sensing by TBK1 controls its phase separation to drive antiviral innate immune responses 通过TBK1感知天冬酰胺控制其相分离来驱动抗病毒先天免疫反应

IF 16 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell

Pub Date : 2026-02-06 DOI: 10.1016/j.molcel.2026.01.010

Jie Du, Chaoqun Li, Li Chai, Fabao Zhao, Lin Lv, Zongcheng Yang, Zhiyuan Zhao, Rong Gong, Liu Yang, Meng Wu, Meng Nie, Jihui Jia, Dongwei Kang, Chengjiang Gao, Wei Zhao, Mutian Jia

引用次数: 0

Molecular basis for anti-jumbo phage immunity by AVAST type 5 AVAST 5型抗巨型噬菌体免疫的分子基础

IF 16 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell

Pub Date : 2026-02-06 DOI: 10.1016/j.molcel.2026.01.004

Aswin Muralidharan, Ana Rita Costa, Desi Fierlier, Daan Frits van den Berg, Halewijn van den Bossche, Adja Damba Zoumaro-Djayoon, Alicia Rodríguez-Molina, Martin Pabst, Martin Pacesa, Bruno E. Correia, Stan J.J. Brouns

引用次数: 0

HSPA1A and DNAJB1 regulate NELF condensate dynamics to safeguard transcriptional recovery under heat stress HSPA1A和DNAJB1调节NELF凝聚动力学，以保障热胁迫下的转录恢复

IF 16 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell

Pub Date : 2026-02-06 DOI: 10.1016/j.molcel.2026.01.015

Shuyao Jiang, Zixuan Jia, Wenxuan Zhu, Yu Liu, Huanyi Fu, Feifeng Zhu, Zhuo Li, Jiaye Yang, Yiying Zhu, Zhongxing Sun, Tianyi Zhu, Xuebo Quan, Huipeng Jiao, Kai Huang, Zhibing Wu, Wei Zou, Bing Yang, Yi Lu, Long Zhang, Fangfang Zhou, Dong Fang, Huasong Lu

Promoter-proximal pausing by negative elongation factor (NELF) establishes a critical checkpoint for RNA polymerase II (RNA Pol II) transcription. Heat shock (HS) induces NELF to form nuclear condensates, yet how their dynamics are regulated and coupled to transcriptional adaptation remains unclear. Using a nanobody-based proximity labeling strategy (NbPro), we identify the molecular chaperones HSPA1A and DNAJB1 as key regulators of NELF condensate dynamics. Although dispensable for initial HS-induced transcriptional repression, chaperone-mediated regulation is required for efficient transcriptional reactivation during recovery. Mechanistically, DNAJB1 recognizes NELFA’s tentacle domain and facilitates HSPA1A recruitment, thereby preventing aberrant aggregation and enabling timely condensate disassembly. Disruption of NELF condensate dynamics leads to persistent NELFA phosphorylation, impaired chromatin association, destabilized RNA Pol II pausing, and premature release of non-productive RNA Pol II complexes. Together, these findings reveal a chaperone-dependent mechanism that governs NELF condensate dynamics and highlight promoter-proximal pausing as a checkpoint to prevent immature RNA Pol II escape, rather than merely a means of transcriptional repression.

负延伸因子（NELF）启动子近端暂停为RNA聚合酶II （RNA Pol II）转录建立了一个关键的检查点。热休克（HS）诱导NELF形成核凝析物，但其动力学是如何调节并与转录适应耦合的尚不清楚。利用基于纳米体的接近标记策略（NbPro），我们确定了分子伴侣HSPA1A和DNAJB1是NELF凝聚动力学的关键调节因子。虽然最初hs诱导的转录抑制是不可缺少的，但伴侣介导的调控对于恢复期间有效的转录再激活是必需的。在机制上，DNAJB1识别NELFA的触手结构域并促进HSPA1A的招募，从而防止异常聚集并使冷凝水及时分解。NELF凝聚动力学的破坏导致持续的NELFA磷酸化，染色质关联受损，RNA Pol II暂停不稳定，以及非生产RNA Pol II复合物的过早释放。总之，这些发现揭示了一种伴侣依赖的机制，该机制控制着NELF凝聚动力学，并突出了启动子-近端暂停作为一个检查点来防止未成熟RNA Pol II逃逸，而不仅仅是一种转录抑制手段。

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引用次数: 0

Collaboration 协作

IF 16 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell

Pub Date : 2026-02-05 DOI: 10.1016/j.molcel.2026.01.016

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Collaboration is essential to scientific progress. As research in molecular biology and related fields becomes more complex, addressing important open questions in the field often requires bringing together labs with expertise in multiple different subject areas and/or technological approaches. To highlight its importance in science, we present a focus issue centered around the theme of collaboration.In the papers we handle and publish, we often see how collaboration directly benefits research.

协作对科学进步至关重要。随着分子生物学和相关领域的研究变得越来越复杂，解决该领域的重要开放性问题往往需要将多个不同学科领域和/或技术方法的专业知识汇集在一起。为了突出其在科学中的重要性，我们提出了一个围绕合作主题的焦点问题。在我们处理和发表的论文中，我们经常看到合作如何直接有利于研究。

引用次数: 0

Epigenetic consequences of DNA damage. DNA损伤的表观遗传后果。

IF 16.6 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell

Pub Date : 2026-02-05 Epub Date: 2026-01-15 DOI: 10.1016/j.molcel.2025.12.029

Tanya T Paull, Patricia L Opresko

Genome regulation is shaped not only by DNA sequence but also by epigenetic mechanisms that influence chromatin structure and gene expression. While epigenetics has classically focused on heritable DNA and histone modifications, growing evidence indicates that certain forms of DNA damage can also generate persistent changes in transcriptional states that are heritable in some scenarios. This review examines how diverse DNA damage-associated processes-including oxidative lesions, R-loops, telomeric damage, DNA double-strand breaks, and poly-ADP-ribosylation-intersect with the epigenome. We highlight the roles of oxidative DNA damage and repair in transcriptional regulation, the contribution of R-loops to gene expression and DNA methylation dynamics, and the impact of telomere-associated damage on chromatin organization and genome maintenance. DNA lesions, and in some cases DNA repair-associated proteins, can thus leave epigenetic "scars" that influence cellular identity, aging, and disease, expanding current views of epigenetic inheritance and genome stability.

基因组调控不仅受DNA序列的影响，还受影响染色质结构和基因表达的表观遗传机制的影响。虽然表观遗传学传统上关注的是可遗传的DNA和组蛋白修饰，但越来越多的证据表明，某些形式的DNA损伤也可以在某些情况下产生可遗传的转录状态的持续变化。这篇综述探讨了不同的DNA损伤相关过程——包括氧化损伤、r环、端粒损伤、DNA双链断裂和多adp核糖基化——如何与表观基因组相交。我们强调了氧化DNA损伤和修复在转录调控中的作用，r环对基因表达和DNA甲基化动力学的贡献，以及端粒相关损伤对染色质组织和基因组维持的影响。因此，DNA损伤，以及在某些情况下DNA修复相关蛋白，可以留下影响细胞身份、衰老和疾病的表观遗传“疤痕”，扩展了当前表观遗传和基因组稳定性的观点。

引用次数: 0

Organizing research at scale: Reflections on leading multi-team scientific collaborations. 组织大规模研究：对领导多团队科学合作的思考。

IF 16.6 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell

Pub Date : 2026-02-05 DOI: 10.1016/j.molcel.2026.01.013

Gene W Yeo

Collaborations are critical features of modern academic science. As biological problems get more complex, larger teams become necessary. However, there is an increased level of friction in coordinating activities and attributing credit in large-scale scientific collaborations. Simple organizational principles and rules of conduct can be powerful lubricants of successful interactions.

合作是现代学术科学的重要特征。随着生物问题变得越来越复杂，更大的团队变得必要。然而，在协调活动和在大规模科学合作中归因功劳方面存在着越来越多的摩擦。简单的组织原则和行为规则可以成为成功互动的强大润滑剂。

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Computational or experimental research? Yes to both! 计算研究还是实验研究？都是！

IF 16.6 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cell

Pub Date : 2026-02-05 DOI: 10.1016/j.molcel.2026.01.017

Hani Goodarzi, Peilong Lu, Noelia Ferruz, Yu Zhou, Aleksandra Kołodziejczyk, Jing-Dong Jackie Han, James K Nuñez

Computational approaches are necessary to leverage the potential of large datasets and generate new hypotheses. At the same time, testing these predictions in biological systems remains key to truly understanding the underlying mechanisms. Once largely siloed, collaboration between bench and computational work is becoming indispensable for many areas of research. For our collaboration focus issue, we spoke with scientists who are integrating different approaches to gain new insights about their experiences in bridging the two.

计算方法对于利用大数据集的潜力和产生新的假设是必要的。同时，在生物系统中测试这些预测仍然是真正理解潜在机制的关键。一旦在很大程度上是孤立的，工作台和计算工作之间的合作在许多研究领域变得不可或缺。对于我们的合作重点问题，我们与正在整合不同方法的科学家进行了交谈，以获得他们在连接两者方面的经验的新见解。

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