title: RPLP1, a crucial ribosomal protein for embryonic development of the nervous system.
abstract: Ribosomal proteins are pivotal to development and tissue homeostasis. RP Large P1 (Rplp1) overexpression is associated with tumorigenesis. However, the physiological function of Rplp1 in mammalian development remains unknown. In this study, we disrupted Rplp1 in the mouse germline and central nervous system (Rplp1CNSΔ). Rplp1 heterozygosity caused body size reductions, male infertility, systemic abnormalities in various tissues and a high frequency of early postnatal death. Rplp1CNSΔ newborn mice exhibited perinatal lethality and brain atrophy with size reductions of the neocortex, midbrain and ganglionic eminence. The Rplp1 knockout neocortex exhibited progenitor cell proliferation arrest and apoptosis due to the dysregulation of key cell cycle and apoptosis regulators (cyclin A, cyclin E, p21CIP1, p27KIP1, p53). Similarly, Rplp1 deletion in pMEFs led to proliferation arrest and premature senescence. Importantly, Rplp1 deletion in primary mouse embryonic fibroblasts did not alter global protein synthesis, but did change the expression patterns of specific protein subsets involved in protein folding and the unfolded protein response, cell death, protein transport and signal transduction, among others. Altogether, we demonstrated that the translation "fine-tuning" exerted by Rplp1 is essential for embryonic and brain development and for proper cell proliferation.
authors: Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Jena, Germany.
authors: Laura
authors: L
authors: Perucho
authors: Oncology and Pathology Group, Institut de Recerca Hospital Vall d'Hebron, Barcelona, Spain.
authors: Ana
authors: A
authors: Artero-Castro
authors: Oncology and Pathology Group, Institut de Recerca Hospital Vall d'Hebron, Barcelona, Spain.
authors: Sergi
authors: S
authors: Guerrero
authors: Oncology and Pathology Group, Institut de Recerca Hospital Vall d'Hebron, Barcelona, Spain.
authors: Santiago
authors: S
authors: Ramón y Cajal
authors: Oncology and Pathology Group, Institut de Recerca Hospital Vall d'Hebron, Barcelona, Spain.
authors: Matilde E
authors: ME
authors: LLeonart
authors: Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), Jena, Germany; Faculty of Biology and Pharmacy, Friedrich Schiller University of Jena, Jena, Germany.
authors: Zhao-Qi
authors: ZQ
authors: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D049628:Body Size; D049109:Cell Proliferation; D002478:Cells, Cultured; D000013:Congenital Abnormalities / Q000209:etiology*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D020043:Genes, Essential; D005804:Genes, Lethal; D007248:Infertility, Male; D008297:Male; D051379:Mice; D009420:Nervous System / Q000196:embryology* / Q000473:pathology; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C000602375:RPLP1 protein, mouse; D012269:Ribosomal Proteins