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Antibody production relies on the tRNA inosine wobble modification to meet biased codon demand.
Giguère, Sophie; Wang, Xuesong; Huber, Sabrina; Xu, Liling; Warner, John; Weldon, Stephanie R; Hu, Jennifer; Phan, Quynh Anh; Tumang, Katie; Prum, Thavaleak; Ma, Duanduan; Kirsch, Kathrin H; Nair, Usha; Dedon, Peter; Batista, Facundo D.
Afiliación
  • Giguère S; The Ragon Institute of Mass General, Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA 02139, USA.
  • Wang X; The Ragon Institute of Mass General, Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA 02139, USA.
  • Huber S; Department of Biological Engineering, MIT, Cambridge, MA 02139, USA.
  • Xu L; The Ragon Institute of Mass General, Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA 02139, USA.
  • Warner J; The Ragon Institute of Mass General, Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA 02139, USA.
  • Weldon SR; The Ragon Institute of Mass General, Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA 02139, USA.
  • Hu J; Department of Biological Engineering, MIT, Cambridge, MA 02139, USA.
  • Phan QA; The Ragon Institute of Mass General, Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA 02139, USA.
  • Tumang K; The Ragon Institute of Mass General, Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA 02139, USA.
  • Prum T; The Ragon Institute of Mass General, Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA 02139, USA.
  • Ma D; BioMicro Center, MIT, Cambridge, MA 02139, USA.
  • Kirsch KH; The Ragon Institute of Mass General, Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA 02139, USA.
  • Nair U; The Ragon Institute of Mass General, Massachusetts Institute of Technology (MIT), and Harvard, Cambridge, MA 02139, USA.
  • Dedon P; Department of Biological Engineering, MIT, Cambridge, MA 02139, USA.
  • Batista FD; Singapore-MIT Alliance for Research and Technology, Singapore 138602.
Science ; 383(6679): 205-211, 2024 01 12.
Article en En | MEDLINE | ID: mdl-38207021
ABSTRACT
Antibodies are produced at high rates to provide immunoprotection, which puts pressure on the B cell translational machinery. Here, we identified a pattern of codon usage conserved across antibody genes. One feature thereof is the hyperutilization of codons that lack genome-encoded Watson-Crick transfer RNAs (tRNAs), instead relying on the posttranscriptional tRNA modification inosine (I34), which expands the decoding capacity of specific tRNAs through wobbling. Antibody-secreting cells had increased I34 levels and were more reliant on I34 for protein production than naïve B cells. Furthermore, antibody I34-dependent codon usage may influence B cell passage through regulatory checkpoints. Our work elucidates the interface between the tRNA pool and protein production in the immune system and has implications for the design and selection of antibodies for vaccines and therapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN de Transferencia / Linfocitos B / Cadenas Pesadas de Inmunoglobulina / Uso de Codones / Inosina / Anticuerpos / Formación de Anticuerpos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN de Transferencia / Linfocitos B / Cadenas Pesadas de Inmunoglobulina / Uso de Codones / Inosina / Anticuerpos / Formación de Anticuerpos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Science Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos