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Ciliates undergo developmentally programmed genome elimination, in which small RNAs direct the removal of transposable elements (TEs) during the development of the somatic nucleus. Twenty-five nucleotide scanRNAs (scnRNAs) are produced from the entire germline genome and transported to the maternal somatic nucleus, where selection of scnRNAs corresponding to germline-specific sequences is thought to take place. Selected scnRNAs then guide the elimination of TEs in the developing somatic nucleus. How germline-specific scnRNAs are selected remains to be determined. Here, we provide important mechanistic insights into the scnRNA selection pathway by identifying a Paramecium homolog of Gtsf1 as essential for the selective degradation of scnRNAs corresponding to retained somatic sequences. Consistently, we also show that Gtsf1 is localized in the maternal somatic nucleus where it associates with the scnRNA-binding protein Ptiwi09. Furthermore, we demonstrate that the scnRNA selection process is critical for genome elimination. We propose that Gtsf1 is required for the coordinated degradation of Ptiwi09-scnRNA complexes that pair with target RNA via the ubiquitin pathway, similarly to the mechanism suggested for microRNA target-directed degradation in metazoans.
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http://dx.doi.org/10.1093/nar/gkae1055 | DOI Listing |
Eur J Neurosci
September 2025
Department of Neuroanatomy, Yokohama City University School of Medicine, Yokohama, Japan.
Pelvic visceromotor functions such as micturition are regulated by coordinated autonomic and somatic motor pathways from the central nervous system. The parasympathetic system induces detrusor muscle contraction while the somatic system facilitates relaxation of the external urethral sphincter, ensuring synchronized and efficient bladder emptying during the voiding process. This study explores the relationship between Barrington's nucleus corticotropin-releasing hormone (CRH)-ergic projections and the formation of perineural nets (PNNs) among spinal motoneurons, particularly parasympathetic preganglionic neurons in the intermediolateral nucleus (IML) and Onuf's nucleus during the maturation of the neural circuitry controlling pelvic visceromotor functions.
View Article and Find Full Text PDFPsychiatry Res Neuroimaging
August 2025
Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
The neural correlates of treatment-resistant depression (TRD) are not fully elucidated. Brainstem functional connectivity (FC) in TRD has rarely been investigated, despite the assumed role of several brainstem nuclei in depression. 23 patients and 23 sex- and age-matched healthy controls underwent resting-state functional MRI.
View Article and Find Full Text PDFNeuron
September 2025
Genomic Analysis Laboratory, Salk Institute, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute, La Jolla, CA 92037, USA.
Somatic mutations alter the genomes of a subset of an individual's brain cells, impacting gene regulation and contributing to disease processes. Mosaic single-nucleotide variants have been characterized with single-cell resolution in the brain, but we have limited information about large-scale structural variation such as whole-chromosome duplication or loss. We used a dataset of over 415,000 single-cell DNA methylation and chromatin conformation profiles from the adult mouse brain to comprehensively identify and characterize aneuploid cells.
View Article and Find Full Text PDFNature
September 2025
Department of Molecular, Cell and Cancer Biology, Genome Integrity Program, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Over time, cells in the brain and in the body accumulate damage, which contributes to the ageing process. In the human brain, the prefrontal cortex undergoes age-related changes that can affect cognitive functioning later in life. Here, using single-nucleus RNA sequencing (snRNA-seq), single-cell whole-genome sequencing (scWGS) and spatial transcriptomics, we identify gene-expression and genomic changes in the human prefrontal cortex across lifespan, from infancy to centenarian.
View Article and Find Full Text PDFEndocrinology
July 2025
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Serotonin (5-hydroxytryptamine; 5-HT) is transported into the human placenta through the serotonin transporter (SERT/SLC6A4) on the surface of the syncytiotrophoblast. During this transit, a significant amount of 5-HT becomes concentrated in the cytotrophoblast nucleus. We used immunochemistry, inhibitors of SERT and transglutaminase 2, and RNA sequencing to elucidate the mechanism and consequences of this nuclear localization.
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