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http://dx.doi.org/10.1126/science.1236645 | DOI Listing |
Nat Commun
December 2024
School of Data Science, The Chinese University of Hong Kong-Shenzhen, Shenzhen, China.
Recently, RNA velocity has driven a paradigmatic change in single-cell RNA sequencing (scRNA-seq) studies, allowing the reconstruction and prediction of directed trajectories in cell differentiation and state transitions. Most existing methods of dynamic modeling use ordinary differential equations (ODE) for individual genes without applying multivariate approaches. However, this modeling strategy inadequately captures the intrinsically stochastic nature of transcriptional dynamics governed by a cell-specific latent time across multiple genes, potentially leading to erroneous results.
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December 2024
Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Sciences, South China Normal University, Guangzhou, China.
The autophagy pathway regulates the degradation of misfolded proteins caused by heat stress (HS) in the cytoplasm, thereby maintaining cellular homeostasis. Although previous studies have established that autophagy (ATG) genes are transcriptionally upregulated in response to HS, the precise regulation of ATG proteins at the subcellular level remains poorly understood. In this study, we provide compelling evidence for the translocation of key autophagy components, including the ATG1/ATG13 kinase complex (ATG1a, ATG13a), PI3K complex (ATG6, VPS34), and ATG8-PE system (ATG5), to HS-induced stress granules (SGs) in Arabidopsis thaliana.
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December 2024
Department of Genetics, Yale University, Yale School of Medicine, New Haven, 06510, CT, USA.
The cis-regulatory elements encoded in an mRNA determine its stability and translational output. While there has been a considerable effort to understand the factors driving mRNA stability, the regulatory frameworks governing translational control remain more elusive. We have developed a novel massively parallel reporter assay (MPRA) to measure mRNA translation, named Nascent Peptide Translating Ribosome Affinity Purification (NaP-TRAP).
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December 2024
Department of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia University Irving Medical Center, New York, NY, USA.
Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.
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December 2024
Laboratory of Retrovirology, The Rockefeller University, New York, NY, 10065, USA.
ZAP is an antiviral protein that binds to and depletes viral RNA, which is often distinguished from vertebrate host RNA by its elevated CpG content. Two ZAP cofactors, TRIM25 and KHNYN, have activities that are poorly understood. Here, we show that functional interactions between ZAP, TRIM25 and KHNYN involve multiple domains of each protein, and that the ability of TRIM25 to multimerize via its RING domain augments ZAP activity and specificity.
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