title: An extraribosomal function of ribosomal protein L13a in macrophages resolves inflammation.
abstract: Inflammation is an obligatory attempt of the immune system to protect the host from infections. However, unregulated synthesis of proinflammatory products can have detrimental effects. Although mechanisms that lead to inflammation are well appreciated, those that restrain it are not adequately understood. Creating macrophage-specific L13a-knockout mice, we report that depletion of ribosomal protein L13a abrogates the endogenous translation control of several chemokines in macrophages. Upon LPS-induced endotoxemia, these animals displayed symptoms of severe inflammation caused by widespread infiltration of macrophages in major organs causing tissue injury and reduced survival rates. Macrophages from these knockout animals show unregulated expression of several chemokines (e.g., CXCL13, CCL22, CCL8, and CCR3). These macrophages failed to show L13a-dependent RNA binding complex formation on target mRNAs. In addition, increased polyribosomal abundance of these mRNAs shows a defect in translation control in the macrophages. Thus, to our knowledge, our studies provide the first evidence of an essential extraribosomal function of ribosomal protein L13a in resolving physiological inflammation in a mammalian host.
authors: Department of Biological, Geological, and Environmental Sciences, Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH 44115, USA.
authors: Darshana
authors: D
authors: Poddar
authors: Abhijit
authors: A
authors: Basu
authors: William M
authors: WM
authors: Baldwin
authors: Roman V
authors: RV
authors: Kondratov
authors: Sailen
authors: S
authors: Barik
authors: Barsanjit
authors: B
authors: Mazumder
mesh_terms: D000818:Animals; D019446:Endotoxemia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004731:Endotoxins / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D010537:Peritoneum / Q000276:immunology / Q000473:pathology; D014176:Protein Biosynthesis / Q000235:genetics; D020218:Response Elements; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000473:pathology
chemical_list: D004731:Endotoxins; D012269:Ribosomal Proteins; C520792:Rpl13a protein, mouse