The gene encoding the ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia. The consequence of these mutations on the onset of the disease remains obscure. Here, we show that RPS19 plays an essential role in biogenesis of the 40S small ribosomal subunit in human cells. Knockdown of RPS19 expression by siRNAs impairs 18S rRNA synthesis and formation of 40S subunits and induces apoptosis in HeLa cells. Pre-rRNA processing is altered, which leads to an arrest in the maturation of precursors to the 18S rRNA. Under these conditions, pre-40S particles are not exported to the cytoplasm and accumulate in the nucleoplasm of the cells in perinuclear dots. Consistently, we find that ribosome biogenesis and nucleolar organization is altered in skin fibroblasts from DBA patients bearing mutations in the RPS19 gene. In addition, maturation of the 18S rRNA is also perturbed in cells from a patient bearing no RPS19-related mutation. These results support the hypothesis that DBA is directly related to a defect in ribosome biogenesis and indicate that yet to be discovered DBA-related genes may be involved in the synthesis of the ribosomal subunits.
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http://dx.doi.org/10.1182/blood-2006-07-038372 | DOI Listing |
Nucleic Acids Res
December 2024
Université de Strasbourg, Architecture et Réactivité de l'ARN, Institut de Biologie Moléculaire et Cellulaire du CNRS, 2 Allée Konrad Roentgen, 67084 Strasbourg, France.
The importance of Mg2+ ions for RNA structure and function cannot be overstated. Several attempts were made to establish a comprehensive Mg2+ binding site classification. However, such descriptions were hampered by poorly modelled ion binding sites as observed in a recent cryo-EM 1.
View Article and Find Full Text PDFNat Commun
January 2025
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, PR China.
Hyperactivation of ribosome biogenesis (RiBi) drives cancer progression, yet the role of RiBi-associated proteins (RiBPs) in breast cancer (BC) is underexplored. In this study, we perform a comprehensive multi-omics analysis and reveal that assembly and maturation factors (AMFs), a subclass of RiBPs, are upregulated at both RNA and protein levels in BC, correlating with poor patient outcomes. In contrast, ribosomal proteins (RPs) do not show systematic upregulation across various cancers, including BC.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center, Houston, TX 77030, USA. Electronic address:
tRNA modifications are critical for several aspects of their functions, including decoding, folding, and stability. Using a multifaceted approach encompassing eCLIP-seq and nanopore tRNA-seq, we show that the human tRNA methyltransferase TRMT1L interacts with the component of the Rix1 ribosome biogenesis complex and binds to the 28S rRNA as well as to a subset of tRNAs. Mechanistically, we demonstrate that TRMT1L is responsible for catalyzing N2,N2-dimethylguanosine (mG) solely at position 27 of tRNA-Tyr-GUA.
View Article and Find Full Text PDFJ Cell Biol
February 2025
Department of Biochemistry, University of Colorado, Boulder, CO, USA.
Cajal bodies are essential sites for the biogenesis of small nuclear and nucleolar ribonucleoproteins. In this issue, Courvan and Parker discuss new work from Neugebauer and colleagues (https://doi.org/10.
View Article and Find Full Text PDFRibosome biogenesis is pivotal in the self-replication of life. In Escherichia coli, three ribosomal RNAs and 54 ribosomal proteins are synthesized and subjected to cooperative hierarchical assembly facilitated by numerous accessory factors. Realizing ribosome biogenesis in vitro is a critical milestone for understanding the self-replication of life and creating artificial cells.
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