近期一些关于核仁的文献（预印本优先发布）：

Chromatin topology control by a muscle-specific ribosomal protein

Three-dimensional genome organization stabilizes cell-type-specific gene expression, yet the tissue-restricted factors that maintain chromatin insulation remain poorly understood. Here, we identify the muscle-specific ribosomal protein Rpl3l as an unexpected nuclear regulator of genome architecture in atrial cardiomyocytes. Rpl3l is enriched in the nucleus and nucleolus, where it binds its own genomic locus and stabilizes a CTCF-anchored chromatin boundary that represses the T-type calcium channel gene Cacna1h. Loss of Rpl3l weakens local chromatin insulation, increases long-range contacts across the Rpl3l-Cacna1h locus, derepresses Cacna1h, and increases susceptibility to atrial fibrillation (AF), which is suppressed by pharmacological inhibition of T-type calcium channels. Furthermore, AF-associated RPL3L variants exhibit impaired nucleolar localization, reduced rRNA binding, and defective repression of CACNA1H in human iPSC-derived atrial cardiomyocytes. Together, these findings reveal a ribosomal protein-chromatin axis linking genome insulation to ion-channel dosage control and cardiac rhythm stability, expanding the repertoire of cell-type-specific genome architecture regulators.

The nucleolar complex FAN-FIP1 mediates ribosome biogenesis in Arabidopsis 拟南芥and is critical for BR signaling and heat tolerance

Ribosome biogenesis is critical for plant development and environmental responses. A large number of ribosomal proteins (RPs) and ribosomal biogenesis factors (RBFs) are required for ribosome biogenesis, many of which remain uncharacterized in plants. We report here the identification of Arabidopsis RBF FAN and its interacting partner FAN-INTERACTING PROTEIN 1 (FIP1). As their human and yeast orthologues, FAN-FIP1 interact. Both FAN and FIP1 participate in the processing of pre-rRNAs. Functional loss of FAN or FIP1 knock-down results in developmental retardation and hypersensitivity to heat stresses. We demonstrate that FAN-FIP1 positively mediates brassinosteroid (BR) 油菜素甾醇 signaling by ensuring the translation efficiency of the BR receptor-coding gene BRASSINOSTEROID INSENSITIVE 1 (BRI1) through the presence of its upstream open reading frame (uORF). Importantly, BR signaling positively mediates the processing of pre-rRNAs, which may be critical not only for development but also for heat tolerance.

The metastasis susceptibility gene RRP1B is a stress-responsive regulator of nuclear RNA processing and splicing in breast cancer

The tumor microenvironment exposes cancer cells to mechanical, thermal, hypoxic, and acidic stresses, yet how cells integrate these signals to remodel RNA processing remains poorly understood. Here, we show that ribosomal RNA Processing 1B (RRP1B), previously characterized as a nucleolar ribosome biogenesis factor and metastasis modifier, functions as a broad-spectrum stress sensor that dynamically repositions among the nuclear envelope, nucleolus, and nuclear speckles (NS). Relocalization is governed by multi-site phosphorylation within intrinsically disordered regions (IDRs): phosphomimetic substitutions promote NS-proximal condensate formation in an RNA-dependent manner, while unphosphorylatable substitutions confine RRP1B to the nucleolus. Under stress, the RRP1B interactome shifts globally, with ribosomal processing partners replaced by pre-mRNA splicing components enriched for NS-resident proteins. RNA immunoprecipitation sequencing (RIP-seq) demonstrates that under basal conditions RRP1B associates with long, intron-rich, nuclear periphery-proximal transcripts, whereas heat shock redirects binding toward shorter, exon-dense transcripts enriched for motifs of serine/arginine-rich (SR) proteins near the NS. RRP1B overexpression nearly abolishes cytoplasmic retained intron accumulation and drives preferential export of specific transcript isoforms in a compartment- and temperature-dependent manner, establishing RRP1B as a regulator of RNA localization fidelity rather than transcriptional output. An RRP1B overexpression signature is most highly activated in basal-like and claudin-low breast tumors, and the RRP1B-associated retained intron splicing program correlates with reduced survival in a tumor-grade-dependent manner. These findings reframe RRP1B as a microenvironmentally sensitive regulator of nuclear RNA processing with direct implications for aggressive breast cancer biology.

A minimal thermodynamic theory for re-entrant liquid-liquid phase separation regulated by small molecules

Small molecules regulate biomolecular condensates in a biphasic manner, promoting liquid–liquid phase separation (LLPS) at low concentrations while suppressing it at higher concentrations. Despite increasing experimental evidence for such re-entrant behavior, a unified physical description remains lacking. Here, we identify a minimal thermodynamic mechanism for re-entrant LLPS by coupling Cahn–Hilliard dynamics to a concentration-dependent Flory interaction parameter containing competing LLPS-promoting and inhibitory contributions. The resulting model reproduces experimentally observed nonmonotonic condensate formation in Tau–tannic acid and TDP-43–bis-ANS systems, including the concentration-dependent emergence and dissolution of protein-rich domains. Spinodal analysis reveals finite concentration windows for phase instability and demonstrates that re-entrant mixing is encoded directly in the free-energy landscape. The framework further captures morphology transitions and diffusive coarsening within the phase-separated regime. These results establish a general mesoscale description of chemically regulated condensates and provide design principles for controlling phase separation through small-molecule modulators.

Cahn-Hilliard动力学是一个描述混合物如何自发分离成不同组分区域（相分离）的数学模型。

这个模型的核心驱动力是系统总是倾向于降低自身的自由能。这里存在两种相互竞争的能量：

体相化学能：这种能量“喜欢”组分分开，让同种物质聚在一起，越纯越好。

界面能：这种能量“讨厌”尖锐的边界，它希望不同组分之间的过渡区域尽量平滑、宽缓，避免陡峭的界面。

当这两种力量达到平衡时，就会形成具有弥散（模糊）界面的相分离结构。这种从均匀状态自发“分家”的过程，在材料科学中被称为旋节分解（Spinodal Decomposition）。

Flory相互作用参数（通常用希腊字母 χ (chi) 表示）是高分子科学和统计热力学中一个极其重要的无量纲参数。它用来定量描述两种不同物质（特别是聚合物和溶剂，或两种不相容的聚合物）之间混合时的相互作用能。简单来说：χ 值决定了两种材料是“喜欢待在一起”（互溶）还是“彼此讨厌”（分离）。

Nuclear basket localized proteasomes maintain circadian 昼夜节律period through nuclear TOC1 proteolysis蛋白水解

Post-translational control of circadian period can involve changes in protein intracellular localization to affect clock function. Many clock proteins rely on a nuclear presence for their activity. As the primary gateway regulating the movement of molecules between the cytosol and the nucleus, the nuclear pore may assist in circadian system maintenance. We describe roles for the nuclear basket proteins, NUA and NUP136, in the maintenance of Arabidopsis circadian period, through effects on the stability of the core clock protein, TOC1. The circadian period of nua and nup136 mutants is significantly longer than that of wildtype plants. We show that NUP136 interacts with NUA, proteasome components and TOC1 in vivo, recruiting them to the inner nuclear rim. TOC1 interaction with the NUP136-NUA complex leads to a proteasome-dependent degradation of TOC1. Loss of NUP136 or NUA disrupts this regulatory environment, leading to aberrant nuclear TOC1 accumulation and consequent lengthening of circadian period. Our work thus identifies nuclear basket-localized proteasomes as key to the maintenance of circadian period.

Rainbow Nucleus Charts Dynamic Interactome of Membrane-less Organelles

Membrane-less organelles (MLOs) perform diverse cellular functions, but how they interact to coordinate these processes remains poorly understood. Here we constructed a “Rainbow Nucleus” cell line to simultaneously visualize five nuclear MLOs using multi-spectral live-cell imaging. We find that MLO interactions are not random: nuclear speckles serve as hubs, and functionally related MLOs interact more frequently than unrelated MLOs. While some interactions are stable, such as those between the histone locus bodies and Cajal bodies, others are transient, such as those between PML nuclear bodies and Cajal bodies. Single particle tracking revealed that stable contacts between Cajal bodies and nuclear speckles are functional, promoting the outward trafficking of small nuclear ribonucleoproteins from Cajal bodies. Finally, RNA Polymerase II-mediated transcription is required to organize the MLO interactome. Our study reveals a structured, transcription-dependent contact network among nuclear MLOs, laying the foundation for future cellular engineering efforts to modulate the MLO interactome.

Chromosomal requirements for formation of multivalent human nucleoli

Human nucleoli are multivalent, involving contributions from up to ten NOR-bearing acrocentric chromosome（着丝粒centromere位于染色体靠近末端的位置，但并没有在最顶端） p-arms. Precision mega-base scale chromosome engineering defines the requirements for this major genome organisational event. NOR deletions reveal that p-arm nucleolar association is rDNA independent. Deletion of all NOR-distal or proximal sequences individually have only a marginal effect on nucleolar association. Finally, deletion of an entire p-arm, while leaving centromere function intact, destroys the nucleolar association potential of that acrocentric. We propose that formation of multivalent nucleoli is not a nucleolar fusion event per se; rather it is driven by the surrounding chromosomal context of NORs.

USP10 Facilitates Homologous Recombination-Mediated DNA Double-Strand Break Repair through Localization to the Nucleolus

Ubiquitin-specific protease 10 (USP10) is a multifunctional deubiquitinating enzyme that primarily regulates cellular stress responses, including the DNA damage response. Here, we show that USP10 is required for homologous recombination (HR)-mediated repair of DNA double-strand breaks (DSBs) and for the maintenance of genomic stability. USP10-depleted cells exhibit spontaneous micronuclei, impaired DSB repair following zeocin and camptothecin treatment, and reduced sister chromatid exchange. These cells are also more sensitive to irradiation and mitomycin C and display increased chromosomal abnormalities after mitomycin C treatment. Persistent RAD51 foci formation in USP10-depleted cells suggests that USP10 functions at a step downstream of RAD51 nucleofilament formation. This function of USP10 in facilitating HR repair depends on deubiquitinase activity but is independent of G3BP1/2 and PABP binding. In addition, a newly identified nucleolar localization signal is required for USP10’s function in DSB repair. Together, these findings indicate that USP10 maintains genome integrity by localizing to the nucleolus and facilitating HR-mediated repair of DSBs.

CHIP, VCP, and Nucleolar Gatekeepers Remodel the Nucleolus into a Stress-Responsive Proteostasis Hub

The nucleolus, classically dedicated to ribosome biogenesis, also acts as a stress-responsive proteostasis hub. During heat shock, misfolded proteins accumulate in its granular component (GC), but whether this is passive or regulated has been unclear. We show that the ubiquitin ligase CHIP remodels the nucleolus into a reversible protein quality control (PQC) compartment by diverting HSP70 from refolding toward sequestration and transiently suppressing rRNA synthesis. This process requires the segregase VCP, which mediates ubiquitinated substrate flux and couples nucleolar PQC with nuclear and ER stress responses. Functional genomics identify NOL6 and WDR55 as intrinsic gatekeepers with opposing effects on sequestration. We further define three structural states - free-flow, peripheral, and sealed - that encode PQC capacity and recovery potential. Thus, nucleolar proteostasis is revealed as an actively regulated continuum, linking chaperones, ubiquitination, and ribosome biogenesis with global stress adaptation.

In-cell structures visualize human pre-ribosome assembly in the nucleolus

Ribosome biogenesis is an essential multi-step process. In eukaryotes, it is orchestrated within the nucleolus, a hallmark multi-layered compartment of the nucleus. Structures of pre-ribosomes have been characterized in vitro, but their assembly pathways within human nucleoli have not been described. Here, we used cryogenic correlative light and electron tomography to visualize the molecular landscapes within HeLa cell nucleoli and obtained in-cell structural snapshots of both ribosomal subunit precursors, the SSU processome and the pre-60S. These recapitulate major states resolved previously in vitro while additionally revealing critical interaction partners, including the RNA exosome, rixosome, and nuclear export receptor CRM1-RanGTP. We further show how pre-ribosome assembly is altered upon RNA polymerase I inhibition. Our study combines molecular structures with cellular context to elucidate the spatiotemporal assembly pathways and regulation of human ribosome biogenesis.

题外话：本期Current Biology对深圳理工大学刘重持教授进行了专访。谈及的一些talk：

What advice do you have for young scientists, including those coming from China?

 I am a strong advocate for finding mentors: not just research advisors but also senior graduate students, acquaintances, friends, and professors from other labs. Mentors can share their experience navigating different career paths and adapting to new environments. I would also encourage students and young scientists to explore and gain experience outside the confines of research laboratories. Seeing the world outside and experiencing new cultures expand one's perspectives and often shape scientific creativity. Finally, remain open-minded and take advantage of new techniques, particularly with computational methods and artificial intelligence. Some of the most important discoveries were made when new tools met old questions.

支持单位：