Biology subjects

Sui, S.

Publications and source records attributed to Sui, S..

5 recordsLinked to original sources

bioRxiv2024

Oligomerization of PRMT1 Regulated RNA-Binding Protein Cascade Promotes Pancreatic Ductal Adenocarcinoma

PRMT1 is the predominant type I protein arginine methyltransferase responsible for generating monomethylarginine and asymmetric dimethylarginine (MMA and ADMA) in various protein substrates. It regulates numerous biological processes, including RNA metabolism, mRNA splicing, DNA damage repair, and chromatin dynamics. The crystal structure of rat PRMT1 has been previously reported as a homodimer; however, higher-order oligomeric species of human PRMT1 have been observed in vivo, and their structural basis remains elusive. In this study, we present the cryo-EM structure of human PRMT1 in its oligomeric form, revealing novel interfaces crucial for PRMT1 self-assembly and normal function. PRMT1 shows a strong preference for intrinsically disordered RGG/RG motifs, which are commonly found in RNA-binding proteins (RBPs), highlighting its critical role in regulating RNA metabolism. In vitro studies indicate that disrupting PRMT1 oligomerization impairs its binding affinity for RGG motif substrates, thereby reducing arginine methylation levels on these substrates. This finding emphasizes the essential role of the oligomeric state of PRMT1 in its function with RGG motif-containing RBPs. In vivo, the loss of PRMT1 oligomerization leads to decreased global ADMA levels in pancreatic ductal adenocarcinoma (PDAC) cells and inhibits PDAC tumor growth. Collectively, we propose that PRMT1 oligomerization, rather than mere dimerization, is sufficient for PRMT1-driven PDAC tumor growth, offering novel insights into the potential therapeutic targeting of PRMT1 oligomeric forms in PDAC. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/627716v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1ed6232org.highwire.dtl.DTLVardef@1c9e688org.highwire.dtl.DTLVardef@3e2c43org.highwire.dtl.DTLVardef@1cbf33e_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

Environmental and Historical Determinants of African Horse Sickness: Insights from Predictive Modeling

This study marks a pioneering effort in analyzing the global epidemiological patterns of African Horse Sickness (AHS) across different regions. By employing predictive modeling with a comprehensive set of environmental variables, we uncovered overarching global patterns in AHS dynamics, a first in this field. Our analysis revealed significant regional differences influenced by specific climatic conditions, highlighting the diseases complexity. The study also identifies new high-risk areas for AHS, underscoring the necessity for regionally tailored disease management strategies. Despite some limitations, such as the exclusion of wild equine data, this research offers critical insights for global AHS intervention and prevention, setting a path for future research incorporating broader datasets and socio-economic factors. Author SummaryAHS presents a significant challenge to the global equine industry, impacting both health and economic aspects. Our study highlights the profound effect of climate change, particularly the frequency of extreme climatic events including temperature and humidity variations, on the transmission dynamics of diseases like AHS. In our research, we focused on overcoming the challenges associated with identifying key environmental factors and determining the appropriate geographic scale for a comprehensive global understanding of AHS. Our aim was to bridge existing knowledge gaps and elucidate the fundamental principles governing AHS transmission. This study establishes a solid foundation for understanding the intricate dynamics of AHS and offers practical pathways for conservation efforts. It emphasizes the urgent need for environmentally conscious strategies to protect horse populations and the industries dependent on them. By highlighting the relationship between environmental factors, vector presence, and AHS transmission, our research underscores the importance of a holistic approach to disease mitigation. In conclusion, the findings of our study not only contribute to the scientific understanding of AHS but also serve as a guide for policymakers and practitioners in developing effective strategies for disease management and prevention, tailored to the specific environmental conditions and challenges faced in different regions around the world.

ecology↗

bioRxiv2023

RNA structures and dynamics with A resolution revealed by x-ray free electron lasers

RNA macromolecules, like proteins, fold to assume shapes that are intimately connected to their broadly recognized biological functions; however, because of their high charge and dynamic nature, RNA structures are far more challenging to determine. We introduce an approach that exploits the high brilliance of x-ray free electron laser sources to reveal the formation and ready identification of [A] scale features in structured and unstructured RNAs. New structural signatures of RNA secondary and tertiary structures are identified through wide angle solution scattering experiments. With millisecond time resolution, we observe an RNA fold from a dynamically varying single strand through a base paired intermediate to assume a triple helix conformation. While the backbone orchestrates the folding, the final structure is locked in by base stacking. In addition to understanding how RNA triplexes form and thereby function as dynamic signaling elements, this new method can vastly increase the rate of structure determination for these biologically essential, but mostly uncharacterized macromolecules.

biophysics↗

bioRxiv2023

Spatiotemporal transcriptome atlas of human embryos after gastrulation

The spatial and temporal atlas of gene expression in the human embryo at early gestation is critical in understanding embryo development, organogenesis, and disease origins. We obtained the spatiotemporal transcriptome from 90 sagittal sections of 16 whole human embryos from 3 to 8 post-conception weeks by Stereo-seq with high resolution and ultra-large field, establishing the development trajectory/regulatory profiling of 49 organs. We uncovered the organ-specific regulons as potential lineage-determining factors and identified the new regulatory networks during heart and brain development. The atlas refines the key organs/cell types vulnerable to virus infection and genetic disorders, and, reveals the dynamics of allelic gene expression in specific organs at different stages. These results present the first comprehensive delineation of the spatiotemporal transcriptomic dynamics of human organogenesis. One Sentence SummaryThe spatiotemporal transcriptome atlas presents a comprehensive delineation of human embryogenesis after gastrulation.

developmental biology↗

bioRxiv2021

Near atomic structure of the inner ring of the Saccharomyces cerevisiae nuclear pore complex

Nuclear pore complexes (NPCs) mediate bidirectional nucleocytoplasmic transport of substances in eukaryotic cells. However, the accurate molecular arrangement of NPCs remains enigmatic owing to their huge size and highly dynamic nature. Here we determined the structure of the asymmetric unit of the inner ring (IR monomer) at 3.73 [A] resolution by single-particle cryo-electron microscopy, and created an atomic model of the intact IR consisting of 192 copies from 8 subunits. In each IR monomer, two approximately parallel rhomboidal structures of the inner and outer layers are sandwiched with the Z-shaped Nup188-Nup192 middle layer and Nup188, Nup192 and Nic96 link all subunits to constitute a relatively stable IR monomer, while the intact IR is assembled by loose and instable interactions between IR monomer. These structures reveal various interaction modes and extensive flexible connections in the assembly, providing a structural basis for the stability and malleability of IR. One-Sentence SummaryAccurate structure of inner ring reveals its assembly and function in dilation and constriction of nuclear pore complex.

biophysics↗