Weekly Research News Digest
This newsletter is designed to share with you research news in various fields where applications of gene sequencing can be found. It will share research findings from Novogene’s customers. By sharing insights from the most prestigious research teams, it is intended to call your attention to the latest applications of sequencing in life sciences and biomedical research and inspire your research.
Welcome back to the Weekly Research News Digest. In this issue, the five articles featured show how researchers approach various issues, including the enhancement of cellular function, virulence factor neutralization, and enzyme expression and catalytic efficiency, with cutting-edge technologies. These studies not only expand our understanding of gene regulation and cellular function recovery, but also offer new strategies and potential for future advancements in areas such as neural regeneration, disease treatment, and crop improvement.
Systematic CRISPR–Cas9 Screening Identifies Genetic Targets to Rejuvenate Neural Stem Cells in Ageing Brains
Neural stem cells (NSCs) in ageing mammalian brains exhibit reduced ability to transit from quiescence to proliferation, which lead to decrease in neurogenesis and defective regeneration after injury. Yet comprehensive research of gene functions in old NSCs had not been done. In a recent study published in Nature, researchers developed in vitro and in vivo CRISPR–Cas9 screening platforms to identify gene knockouts enhancing NSC activation in aged mice. They found over 300 gene knockouts that specifically reinitiate activation in aged NSCs, the key ones associated with cilium organization and glucose metabolism. They showed that knocking out Slc2a4, which encodes GLUT4 glucose transporter, enhances NSC function. They also discovered that transient glucose starvation restores NSC activation. These findings highlight glucose metabolism's role in NSC decline and suggest potential interventions for ageing-related declines.
Phase Separation Links RNA m6A Modification with miRNA Processing
The methyltransferase complex (MTC) and the microprocessor are responsible for RNA m6A modification and microRNA production, respectively. Yet the potential cross-regulation between these two distinct complexes has been largely unexplored. Researchers from China and the U.S. found that SERRATE (SE), a microprocessor component, forms liquid-like condensates that increase the solubility and stability, and thereby, the activity, of MTC subunit B. MTC, in turn, recruits the microprocessor to the MIRNA loci for co-transcriptional cleavage of primary miRNA substrates. Additionally, m6A-modified primary miRNAs substrates are attracted by m6A readers, which retain the microprocessor for further processing. This study reveals a novel regulatory mechanism involving phase separation through MTC and microprocessor coordination.
Type IV-A1 CRISPR–Cas: A Natural Tool for Gene Regulation and Plasmid Control
Type IV CRISPR–Cas effector complexes, commonly found on plasmids, are thought to inhibit competing plasmid replication. The Type IV-A1 CRISPR–Cas system in Pseudomonas oleovorans consists a CRISPR RNA (crRNA) that tightly controls the expression of a chromosomal target, acting as a natural CRISPR interference (CRISPRi) mechanism. Researchers investigated the CRISPRi effects of this system leveraging synthetic crRNAs designed to target genomic and plasmid sequences. They reported that experiments targeting reporter genes revealed widespread interference in P. oleovorans and Escherichia coli cells producing recombinant CRISPR ribonucleoprotein (crRNP) complexes. RNA sequencing (RNA-seq) analysis showed that Type IV-A1 CRISPRi effectively downregulated the histidine operon over a broad range, whereas dCas9-based CRISPRi effects were confined to regions near its binding site. Single-molecule microscopy revealed the dynamic localization of crRNP complexes, with fluorescently labeled crRNPs clustering in areas of increased plasmid replication, confirming efficient plasmid targeting. These findings establish the Type IV-A1 system as a robust tool for regulating gene expression and controlling plasmid replication.
Pan-Specific Mini-Proteins for Neutralizing Clostridioides difficile Toxin B Variants
Clostridioides difficile toxin B (TcdB) is a major virulence factor in C. difficile infections. Neutralizing its diverse variants with a universal solution is challenging. According to a recent study published in Nature Communications, researchers from Westlake University designed a pan-specific mini-protein binders targeting major subtypes of TcdB. They demonstrated that the binders specifically interact with the first receptor-binding interface (RBI-1) of different TcdB subtypes, exhibiting binding affinities ranging from 20 pM to 10 nM. When combined with CSPG4, engineered and evolved variants of the mini-protein binder neutralize major TcdB variants both in cells and in vivo more effectively. These mini-proteins provide a promising option for developing universal therapeutics against C. difficile infections.
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Genetic Insights into DMSP Synthesis in Spartina anglica Reveal Potential for Bioengineering Stress-Resilient Crops
Dimethylsulfoniopropionate (DMSP) plays a critical role in stress protection, global sulfur cycling, and chemotaxis. It is also a major source of climate-active gases. Spartina cordgrasses is known for producing unusually high levels of DMSP, which makes saltmarshes key global sites for DMSP cycling. A research team from the University of East Anglia in the UK investigated genes involved in DMSP synthesis in Spartina anglica. They identified genes associated with high-level DMSP synthesis, including methionine S-methyltransferase, S-methylmethionine decarboxylase, and DMSP-amine oxidase. They found that while homologous enzymes are common across plants, differences in their expression and catalytic efficiency explain difference in accumulated concentrations of DMSP between S. anglica and other plants. These findings show that administration of DMSP enhances plant tolerance to salinity and drought, providing a potential option for agricultural breeding.
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About Novogene
Novogene specializes in the application of advanced molecular biotechnology and high-performance computing in the research fields of life science and human health. Established in March 2011, Novogene strives to become a global leader in providing genetic science services and technology products. Novogene has set up operations and laboratories in the United States, the United Kingdom, Netherlands, Germany, as well as in China, Singapore and Japan.
Novogene has served over 7,300 global customers, covering 90 countries and regions across 6 continents. It has cooperated extensively with many academic institutions and completed several advanced-level, international genomics research projects. By 2023, Novogene has co-published and/or been acknowledged in more than 22,850 articles in Science Citation Index, with an accumulative impact factor of more than 148,250.
Novogene's partners are worldwide and include more than 4,200 scientific research institutions and universities, more than 680 hospitals and over 2,400 pharmaceutical and agricultural enterprises. Currently, Novogene has obtained 425 software copyrights and 76 patents.
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