Article
Biology
M. Julhasur Rahman, Sherry L. Haller, Ana M. M. Stoian, Jie Li, Greg Brennan, Stefan Rothenburg
Summary: This study developed a model to understand the mechanisms of gene transfer in vaccinia virus. The findings indicate that gene capture events are mediated by LINE-1 retrotransposition and highlight the role of host retrotransposons as major drivers for virus evolution.
Editorial Material
Cell Biology
Mahsa Shahidi Dadras, Howard A. Fine
Summary: An ependymoma subtype is caused by fusion proteins associated with YAP1, which are localized within nuclear condensates and play a crucial role in tumor formation by activating various oncogenic mechanisms.
NATURE CELL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Zhenkun Na, Yang Luo, Danica S. Cui, Alexandra Khitun, Stephanie Smelyansky, J. Patrick Loria, Sarah A. Slavoff
Summary: Proteogenomic analysis in humans has uncovered numerous microproteins, with many remaining uncharacterized, lacking secondary structure, and having limited evolutionary conservation. Among them, NBDY, an intrinsically disordered microprotein, has been shown to undergo liquid-liquid phase separation and remixing through phosphorylation, regulating P-body dynamics during cell proliferation. This suggests that microproteins may play a role in liquid-liquid phase separation and remixing behavior to impact cellular processes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Physics, Multidisciplinary
Leonardo Demarchi, Andriy Goychuk, Ivan Maryshev, Erwin Frey
Summary: Enzyme-enriched condensates can regulate the distribution of their substrates and induce enzyme fluxes through feedback interactions. Weak feedback leads to condensate movement towards the center of a confined domain, while above a threshold, self-propulsion and oscillatory dynamics occur. Enzyme-driven fluxes can also result in interrupted coarsening and condensate division, leading to equidistant positioning.
PHYSICAL REVIEW LETTERS
(2023)
Review
Biochemistry & Molecular Biology
Yi Zhang, Geeta J. Narlikar, Tatiana G. Kutateladze
Summary: Biological enzymes accelerate chemical reactions in living organisms, and the complex environment within cells is a major regulator of enzyme activity. Biological condensates, formed spontaneously through phase separation, offer new possibilities for modulating enzymatic reactions.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jack O. Law, Carl M. Jones, Thomas Stevenson, Thomas A. Williamson, Matthew S. Turner, Halim Kusumaatmaja, Sushma N. Grellscheid
Summary: Interfacial tension is important for droplet coalescence and interaction with lipid membranes. A model based solely on interfacial tension is inadequate for describing stress granules in live cells, which exhibit elastic bending deformation. Stress granules have an irregular, nonspherical shape and are viscoelastic droplets with a structured interface. Different types of stress granules can only be differentiated through large-scale surveys.
Article
Physics, Multidisciplinary
Pierre Ronceray, Yaojun Zhang, Xichong Liu, Ned S. Wingreen
Summary: Multivalent associative proteins are essential for phase separation in intracellular liquid condensates. This study investigates the internal dynamics of bond-network condensates composed of two complementary proteins through scaling analysis and molecular dynamics. The findings reveal that when the stoichiometry is balanced, relaxation significantly slows down due to a lack of alternative binding partners, which strongly influences bulk diffusivity, viscosity, and mixing. This provides an experimental means to test the prediction.
PHYSICAL REVIEW LETTERS
(2022)
Editorial Material
Biophysics
Ashish Joshi, Samrat Mukhopadhyay
Summary: The formation of biomolecular condensates is a new biophysical principle for subcellular compartmentalization, enabling the regulation of complex biomolecular reactions. This Research Highlight summarizes papers published in Biophysical Journal from 2021 to 2022, which provide insights into the formation of biomolecular condensates through protein phase separation with or without nucleic acids.
BIOPHYSICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Tanja Mittag, Aseem Z. Ansari
Summary: A spectrum of high-risk leukemias is caused by recurrent chromosomal translocations that result in the expression of fusion proteins. The oncogenic properties of one such fusion, NUP98-HOXA9, are linked to its ability to self-associate and function through aberrantly phase-separated onco-condensates.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Physical
Kamal Bhandari, Michael A. Cotten, Jonggul Kim, Michael K. Rosen, Jeremy D. Schmit
Summary: Biomolecular condensates are formed by the assembly of multivalent molecules, creating phase-separated networks that recruit client molecules to provide functionality. The network structure plays a key role in defining client recruitment and functionality, with filamentous structures constraining scaffold stoichiometries and client recruitment site distribution. These interactions within liquid states can be disordered yet still contain structural features that contribute to the functionality of the condensate.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biology
Aniruddha Chattaraj, Michael L. Blinov, Leslie M. Loew
Summary: Research shows that biomolecular condensates are formed by liquid-liquid phase separation of multivalent molecules, and their concentration dependence is regulated by buffering and the solubility product constant. The role of these factors differs between homotypic and heterotypic systems.
Article
Chemistry, Physical
Divya Kota, Huan-Xiang Zhou
Summary: This study found that macromolecular regulators have effects on the material properties of biomolecular condensates, including phase equilibrium, interfacial tension, viscoelasticity, fusion speed, etc. These results illustrate the opportunities for tuning material properties.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
Andrew Z. Lin, Kiersten M. Ruff, Furqan Dar, Ameya Jalihal, Matthew R. King, Jared M. Lalmansingh, Ammon E. Posey, Nadia A. Erkamp, Ian Seim, Amy S. Gladfelter, Rohit V. Pappu
Summary: The authors report that protein-RNA condensates with shared proteins and distinct RNAs can form and persist in vitro and in cells as distinct entities if the nonshared RNA molecules are dynamically arrested, but the shared protein components are dynamically exchangeable.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Juyoung Son, Yongwon Jung
Summary: In this study, stable protocells with an uptake ability for outside biomolecules were successfully constructed using protein-based liquid condensates and a lipid coating. These protocells, which have high condensate rigidity and specific protein-lipid interactions, can selectively uptake various outside proteins through specific protein interactions.
Article
Multidisciplinary Sciences
Bryan A. Gibson, Claudia Blaukopf, Tracy Lou, Lifeng Chen, Lynda K. Doolittle, Ilya Finkelstein, Geeta J. Narlikar, Daniel W. Gerlich, Michael K. Rosen
Summary: Eukaryotic nuclear DNA is wrapped around histone proteins to form nucleosomes on a chromatin fiber. The folding and compaction of chromatin regulate essential processes like transcription and chromosome segregation. Our understanding of how chromatin can be dynamically remodeled in highly compacted states is limited.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
J. Ignacio Gutierrez, Gregory P. Brittingham, Yonca Karadeniz, Kathleen D. Tran, Arnob Dutta, Alex S. Holehouse, Craig L. Peterson, Liam J. Holt
Summary: It is increasingly recognized that changes in intracellular pH serve as important biological signals. This study focuses on elucidating the molecular mechanisms of pH sensing. The researchers found that a nucleocytoplasmic pH oscillation is crucial for the transcriptional response to carbon starvation in Saccharomyces cerevisiae. They also discovered that the SWI/SNF chromatin remodeling complex plays a key role in this response. Specifically, a glutamine-rich low-complexity domain (QLC) in the SNF5 subunit of this complex, along with histidines within this domain, is essential for efficient transcriptional reprogramming. Additionally, the SNF5 QLC is responsible for the pH-dependent recruitment of SWI/SNF to an acidic transcription factor in a reconstituted nucleosome remodeling assay. Simulations revealed that the protonation of histidines in the SNF5 QLC causes conformational expansion, offering a potential biophysical mechanism for regulating these interactions. Overall, this study suggests that pH changes act as a second messenger for transcriptional reprogramming during carbon starvation, with the SNF5 QLC serving as a pH sensor.
Article
Physics, Multidisciplinary
Baptiste Alric, Cecile Formosa-Dague, Etienne Dague, Liam J. Holt, Morgan Delarue
Summary: The study reveals that cellular growth in confined spaces leads to mechanical compressive stress, which in turn decreases cell growth. This growth-induced pressure is accompanied by an increase in a cellular physical property called macromolecular crowding. The researchers develop a model that explains how increased macromolecular crowding hinders protein expression and reduces cell growth, without the need for specific molecular sensors or signaling cascades. This mechanism could be a conserved feedback loop that allows cells to sense their environment based on their physical properties.
Article
Multidisciplinary Sciences
Wilson McKerrow, Xuya Wang, Carlos Mendez-Dorantes, Paolo Mita, Song Cao, Mark Grivainis, Li Ding, John LaCava, Kathleen H. Burns, Jef D. Boeke, David Fenyo
Summary: LINE-1, an active retrotransposon, is derepressed in many cancers and is correlated with p53 mutation and copy number alteration. It induces replication stress and is associated with the DNA damage response pathway in endometrial cancer.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Aaron N. Brooks, Amanda L. Hughes, Sandra Clauder-Muenster, Leslie A. Mitchell, Jef D. Boeke, Lars M. Steinmetz
Summary: This study investigates the effects of sequence features and transcriptional context on RNA transcript isoform expression. Using synthetic yeast strains with rearranged genes, the researchers discovered that neighboring transcription also influences gene expression levels and transcript isoform boundaries. They identified features of transcriptional context that can predict these alterations and successfully engineered a synthetic circuit where transcript length is controlled by neighboring transcription.
Article
Multidisciplinary Sciences
Weimin Zhang, Ran Brosh, Laura H. McCulloch, Yinan Zhu, Hannah Ashe, Gwen Ellis, Brendan R. Camellato, Sang Yong Kim, Matthew T. Maurano, Jef D. Boeke
Summary: This study presents a new conditional knockout strategy that enables efficient counter selection in mouse embryonic stem cells. The strategy overwrites counter selectable markers and allows the removal or replacement of wild-type DNA with the desired payload DNA. The restored native gene function in the conditional knockout cells facilitates subsequent mouse development and the generality of the strategy is demonstrated through the knockout of other genes.
Article
Biochemistry & Molecular Biology
Dajun Sang, Tong Shu, Christian F. Pantoja, Alain Ibanez de Opakua, Markus Zweckstetter, Liam J. Holt
Summary: Phase separation can concentrate biomolecules and accelerate reactions. By engineering phosphorylation reactions within synthetic condensates, this study found that phosphorylation dynamics are rapid within condensates and can drive cell localization changes. High client concentration and the availability of many excess client-binding sites are crucial for efficient phosphorylation within condensates, and macromolecular crowding also modulates phosphorylation. This study provides important insights into cellular signaling mechanisms.
Editorial Material
Biochemistry & Molecular Biology
Liam Joseph Holt, Lance T. Denes
Summary: Volume control is a fundamental challenge for cells, and the mechanisms behind it have been a topic of debate. A recent study has found that increased molecular crowding leads to the condensation of WNK kinase, enabling cells to sense and respond to a decrease in cell volume.
Article
Biochemistry & Molecular Biology
Wilson McKerrow, Larisa Kagermazova, Nicole Doudican, Nicholas Frazzette, Efiyenia Ismini Kaparos, Shane A. Evans, Azucena Rocha, John M. Sedivy, Nicola Neretti, John Carucci, Jef D. Boeke, David Fenyo
Summary: LINE-1 retrotransposons are sequences capable of copying themselves to new genomic loci via an RNA intermediate. New studies using the method-5 ' scL1seq have identified LINE-1 expression in human epithelial cells and mouse hippocampal neurons, in addition to its known expression in tumors. The findings also suggest a modest increase in LINE-1 expression with age, supporting its association with age-related diseases.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yu Zhao, Camila Coelho, Stephanie Lauer, Milosz Majewski, Jon M. Laurent, Ran Brosh, Jef D. Boeke
Summary: The use of synthetic genomics has revolutionized our ability to answer fundamental biological questions by designing and building "big" DNA constructs. Saccharomyces cerevisiae, or budding yeast, is a powerful platform for assembling large synthetic constructs, but introducing designer variations to episomal assemblies remains challenging. The CRISPR Engineering of EPisomes in Yeast (CREEPY) method provides a rapid and efficient way to edit large synthetic episomal DNA constructs.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Makiha Fukuda, Jitong Cai, Joel S. Bader, Jef D. Boeke
Summary: A synthetic biology approach to constructing an RNA-based genome expands our understanding of living things and opens avenues for technological advancement. Understanding the structure-function relationships of RNA sequences is critical for the precise design of an artificial RNA replicon.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Cell Biology
Martina Bonucci, Tong Shu, Liam J. Holt
Summary: The article reviews how the crowded and active intracellular environment affects the motion and assembly of macromolecules, emphasizing the impact of these changes on physiology and signaling, and their potential contribution to aging and diseases.
TRENDS IN CELL BIOLOGY
(2023)
Article
Neurosciences
Paul W. Frazel, David Labib, Theodore Fisher, Ran Brosh, Nicolette Pirianian, Anne Marchildon, Jef D. Boeke, Valentina Fossati, Shane A. Liddelow
Summary: Researchers used single-cell/single-nucleus RNA sequencing to analyze the differentiation of macroglia in the brain and spinal cord. They identified candidate genes involved in glial cell fate specification and observed heterogeneous expression of astrocyte surface markers during differentiation. The researchers also optimized a mouse astrocyte differentiation protocol and explored potential genomic regulatory sites mediating glial differentiation using multi-omic analysis.
NATURE NEUROSCIENCE
(2023)
Article
Genetics & Heredity
Guojon Olafsson, Max A. B. Haase, Jef D. Boeke
Summary: This study demonstrates that the differences in protein composition from different species may lead to complementation failure during mitosis.
G3-GENES GENOMES GENETICS
(2023)