Multiple RNA Surveillance Mechanisms Cooperate to Reduce the Amount of Nonfunctional Igκ Transcripts
| Autor: | Guillaume Chemin, Michel Cogné, Aurélien Tinguely, Fabien Lechouane, Sophie Duchez, Laurent Delpy, Christophe Sirac |
|---|---|
| Přispěvatelé: | Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Université de Limoges (UNILIM) |
| Rok vydání: | 2010 |
| Předmět: |
Transcription
Genetic MESH: Gene Rearrangement B-Lymphocyte Light Chain MESH: Codon Terminator MESH: Down-Regulation Mice 0302 clinical medicine Transcription (biology) Gene Rearrangement B-Lymphocyte Light Chain Immunology and Allergy MESH: Animals MESH: Codon Nonsense Frameshift Mutation Recombination Genetic Genetics MESH: Plasma Cells 0303 health sciences Stem Cells MESH: Frameshift Mutation Cell Differentiation medicine.anatomical_structure Codon Nonsense RNA splicing Codon Terminator [SDV.IMM]Life Sciences [q-bio]/Immunology MESH: Recombination Genetic MESH: Cell Differentiation MESH: Cell Line Tumor RNA Splicing Plasma Cells Immunology MESH: Immunoglobulin kappa-Chains Down-Regulation MESH: Stem Cells Biology Frameshift mutation Immunoglobulin kappa-Chains 03 medical and health sciences Cell Line Tumor medicine Animals RNA Messenger MESH: Mice Gene Alleles B cell MESH: RNA Messenger 030304 developmental biology Messenger RNA MESH: Alleles MESH: Transcription Genetic RNA surveillance Open reading frame MESH: RNA Splicing 030215 immunology |
| Zdroj: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2010, 184 (9), pp.5009-17. ⟨10.4049/jimmunol.0902949⟩ |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Random V(D)J junctions ensure that the diversity of the Ig primary repertoire is adapted to the vast heterogeneity of Ags. In two-thirds of cases, recombination between variable segments induces a frameshift in the open reading frame and generates a premature termination codon. In B cells harboring biallelic V(D)J rearrangement of Ig genes, transcription is known to occur on both the functional and nonfunctional alleles, generating considerable amounts of primary transcripts with out-of-frame V regions. In this study, we analyzed in cell lines and primary B cells the RNA surveillance of nonfunctional Igκ transcripts arising from nonproductive rearrangement. We demonstrated that splicing inhibition, nonsense-mediated decay and nonsense-altered splicing each have an individual partial effect that together associate into an efficient surveillance machinery, downregulating nonfunctional Igκ mRNA. Moreover, we provide evidence that the RNA surveillance efficiency increases throughout B cell development. Whereas splicing inhibition remains constant in most cell lines, differences in nonsense-mediated decay and nonsense-altered splicing are responsible for the higher RNA surveillance observed in plasma cells. Altogether, these data show that nonfunctionally rearranged alleles are subjected to active transcription but that multiple RNA surveillance mechanisms eradicate up to 90% of out-of-frame Igκ mRNA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|