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U6 snRNA is a catalytic RNA responsible for pre-mRNA splicing reactions and undergoes various post-transcriptional modifications during its maturation process. The 3'-oligouridylation of U6 snRNA by the terminal uridylyltransferase, TUT1, provides the Lsm-binding site in U6 snRNA for U4/U6 di-snRNP formation and this ensures pre-mRNA splicing. Here, we present the crystal structure of human TUT1 (hTUT1) complexed with U6 snRNA, representing the post-uridylation of U6 snRNA by hTUT1. The N-terminal ZF-RRM and catalytic palm clamp the single-stranded AUA motif between the 5'-short stem and the 3'-telestem of U6 snRNA, and the ZF-RRM specifically recognizes the AUA motif. The ZF and the fingers hold the telestem, and the 3'-end of U6 snRNA is placed in the catalytic pocket of the palm for oligouridylation. The oligouridylation of U6 snRNA depends on the internal four-adenosine tract in the 5'-part of the telestem of U6 snRNA, and hTUT1 adds uridines until the internal adenosine tract can form base-pairs with the 3'-oligouridine tract. Together, the recognition of the specific structure and sequence of U6 snRNA by the multi-domain TUT1 protein and the intrinsic sequence and structure of U6 snRNA ensure the oligouridylation of U6 snRNA.
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http://dx.doi.org/10.1038/s41467-023-40420-9 | DOI Listing |
Plant Mol Biol
March 2025
Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Nara, 630-0192, Japan.
Alternative pre-mRNA splicing (AS) is a crucial regulatory layer of gene expression in eukaryotes. AS patterns can change in response to abiotic and biotic stress, allowing cellular functions to adapt to environmental conditions. Here, we examined the effects of cellular stress-inducing chemicals on AS-mediated gene regulation in Arabidopsis thaliana by investigating the alternatively spliced forms of SERINE-ARGININE PROTEIN30 (SRp30) and U1-70 K, encoding splicing factors, as well as ASCORBATE PEROXIDASE3 (APX3) and FOLYLPOLYGLUTAMATE SYNTHASE3 (FPGS3), encoding enzymes important for stress responses.
View Article and Find Full Text PDFG3 (Bethesda)
March 2025
Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109 USA.
RNA interference is a conserved silencing mechanism that depends on the generation of small RNA molecules that leads to the degradation of the targeted mRNAs. Nuclear RNA interference is a unique process that triggers regulation through epigenetic alterations to the genome. This pathway has been extensively characterized in Caenorhabditis elegans and involves the nuclear recruitment of H3K9 histone methyltransferases by the Argonautes HRDE-1 and NRDE-3.
View Article and Find Full Text PDFStem Cell Reports
March 2025
Department of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA, USA. Electronic address:
Spermatogenesis is driven by dramatic changes in chromatin regulation, gene transcription, and protein expression. To assess the mechanistic bases for these developmental changes, we utilized multiomic single-cell/nucleus RNA sequencing (sc/snRNA-seq) and single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq) to identify chromatin changes associated with transcription in adult mouse and rat testes. We characterized the relationships between the transcriptomes and chromatin of both species, including the divergent expression of Id4 in spermatogonial stem cells between species.
View Article and Find Full Text PDFBone Joint Res
March 2025
Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Aims: Osteoarthritis (OA) is a common degenerative disease that leads to pain, disability, and reduced quality of life. Orientin exhibits considerable anti-inflammatory and antioxidative properties, but its role in chondrocyte senescence and OA progress has not yet been fully characterized. The aim of this study was to evaluate the protective effects of orientin on OA.
View Article and Find Full Text PDFTheranostics
March 2025
Department of Thyroid and Neck Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300040, China.
Anaplastic thyroid carcinoma (ATC) is an extraordinarily aggressive form of thyroid cancer, frequently presenting with locally advanced infiltration or distant metastases at the time of initial diagnosis, thus missing the optimal window for surgical intervention. Consequently, systemic chemotherapy and targeted therapies are vital for improving the prognosis of ATC. However, ATC exhibits significant resistance to conventional treatments, highlighting the need to elucidate the biological mechanisms underlying this drug resistance and identify novel therapeutic targets to overcome it.
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