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Alternative splicing (AS) plays an essential role in development, differentiation and carcinogenesis. However, the mechanisms underlying splicing regulation during mouse embryo gastrulation remain unclear. Based on spatial-temporal transcriptome and epigenome data, we detected the dynamics of AS and revealed its regulatory mechanisms across primary germ layers during mouse gastrulation, spanning developmental stages from E6.5 to E7.5. Subsequently, the dynamic expression of splicing factors (SFs) during gastrulation was characterized, while the expression patterns and functions of germ layer-specific SFs were identified. The results indicate that AS and differential alternative splicing events (DASEs) exhibit dynamic changes and are significantly abundant during the late stage of gastrulation. Similarly, SFs demonstrate stage-specific expression, with elevated levels observed during the middle and late stages of gastrulation. Epigenetic signals associated with SFs and AS sites demonstrate significant enrichment and undergo dynamic changes throughout gastrulation. Overall, this study offers a systematic analysis of AS during mouse gastrulation, identifies primary germ layer-specific AS events, and characterizes the expression patterns of SFs and the associated epigenetic signals. These findings enhance the understanding of the mechanisms underlying the formation of the three germ layers during mammalian gastrulation, with a focus on pre-mRNA AS.
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http://dx.doi.org/10.1038/s41598-025-96148-7 | DOI Listing |
Genome Res
September 2025
College of Life Science, Sichuan Agricultural University, Ya'an, 625014, People's Republic of China;
Poultry egg production is shaped by the intertwined action of multiple physiological systems, greatly magnifying the complexity of its underlying genetic regulation. Although multitissue mapping of regulatory variants offers a powerful route to untangle this complexity, comprehensive data sets in ducks remain scarce. Meanwhile, the contributions of peripheral systems beyond neuroendocrine regulation on poultry egg production are still largely unexplored.
View Article and Find Full Text PDFJ Neurosci
September 2025
College of Life Sciences, Zhejiang University, Hangzhou 310058, P.R. China
Nonsense-mediated mRNA decay (NMD) is a conserved RNA surveillance mechanism that degrades transcripts with premature termination codons (PTCs) and finetunes gene expression by targeting RNA transcripts with other NMD inducing features. This study demonstrates that conditional knockout of , a key NMD component, in oligodendrocyte lineage cells disrupts the degradation of PTC-containing transcripts, including aberrant variants of the RNA-binding protein The loss of SMG5 in both sexes of mice impaired oligodendrocyte differentiation, reduced myelin gene expression, and led to thinner myelin sheaths and compromised motor function in mice. Mechanistically, HNRNPL was shown to regulate the alternative splicing of myelin-associated genes and , and promote oligodendrocyte differentiation.
View Article and Find Full Text PDFGenomics
September 2025
Laboratory of Single Cell Analyses, Institute of Bioorganic Chemistry Polish Academy of Sciences, Zygmunta Noskowskiego str. 12/14, 61-704 Poznań, Poland. Electronic address:
Despite advancements in genome annotation tools, challenges persist for non-classical model organisms with limited genomic resources, such as Schmidtea mediterranea. To address these challenges, we developed a flexible and scalable genome annotation pipeline that integrates short-read (Illumina) and long-read (PacBio) sequencing technologies. The pipeline combines reference-based and de novo assembly methods, effectively handling genomic variability and alternative splicing events.
View Article and Find Full Text PDFBiotechnol Adv
September 2025
Key Laboratory of Microbiological Metrology, Measurement & Bio-product Quality Security, State Administration for Market Regulation, China Jiliang University, Hangzhou 310018, China. Electronic address:
Nanopore direct RNA sequencing (DRS) is a transformative technology that enables full-length, single-molecule sequencing of native RNA, capturing transcript isoforms and preserving epitranscriptomic modifications without cDNA conversion. This review outlines key advances in DRS, including optimized protocols for mRNA, rRNA, tRNA, circRNA, and viral RNA, as well as analytical tools for isoform quantification, poly(A) tail measurement, fusion transcript identification, and base modification profiling. We highlight how DRS has redefined transcriptomic studies across diverse systems-from uncovering novel transcripts and alternative splicing events in cancer, plants, and parasites to enabling the direct detection of m6A, m5C, pseudouridine, and RNA editing events.
View Article and Find Full Text PDFEMBO J
September 2025
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
During a critical period of postnatal brain development, neural circuits undergo significant refinement coincident with widespread alternative splicing of hundreds of genes, which undergo altered splice site selection for the generation of isoforms essential for synaptic plasticity. Here, we reveal that neuronal activity-dependent phosphorylation of paxillin at its serine 119 (p-paxillin) acts as a molecular switch in the nucleus for the control of alternative splicing during this period. We show that following NMDA receptor activation, nuclear p-paxillin is recruited to nuclear speckles, where it interacts with splicing factors, such as U2AFs.
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