دورية أكاديمية
أعرض في EDS

RNA 2'-O-methylation promotes persistent R-loop formation and AID-mediated IgH class switch recombination.

التفاصيل البيبلوغرافية
العنوان: RNA 2'-O-methylation promotes persistent R-loop formation and AID-mediated IgH class switch recombination.
المؤلفون: Kassab MA; Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA. muzaffer.kassab@pennmedicine.upenn.edu.; Present address: Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. muzaffer.kassab@pennmedicine.upenn.edu., Chen Y; Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.; Present address: Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA., Wang X; Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.; Present address: Westlake University, Hangzhou, Zhejiang, P. R. China., He B; Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.; Present address: Division of Cellular and Developmental Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94705, USA., Brown EJ; Present address: Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA., Yu X; Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA. yuxiaochun@westlake.edu.cn.; Present address: Westlake University, Hangzhou, Zhejiang, P. R. China. yuxiaochun@westlake.edu.cn.
المصدر: BMC biology [BMC Biol] 2024 Jul 08; Vol. 22 (1), pp. 151. Date of Electronic Publication: 2024 Jul 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101190720 Publication Model: Electronic Cited Medium: Internet ISSN: 1741-7007 (Electronic) Linking ISSN: 17417007 NLM ISO Abbreviation: BMC Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, c2003-
مواضيع طبية MeSH: Immunoglobulin Class Switching*/genetics , Cytidine Deaminase*/metabolism , Cytidine Deaminase*/genetics , Cytidine Deaminase*/chemistry , R-Loop Structures*, Animals ; Mice ; Methylation ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Heavy Chains/metabolism ; Recombination, Genetic ; RNA/metabolism ; RNA/genetics
مستخلص: Background: RNA-DNA hybrids or R-loops are associated with deleterious genomic instability and protective immunoglobulin class switch recombination (CSR). However, the underlying phenomenon regulating the two contrasting functions of R-loops is unknown. Notably, the underlying mechanism that protects R-loops from classic RNase H-mediated digestion thereby promoting persistence of CSR-associated R-loops during CSR remains elusive.
Results: Here, we report that during CSR, R-loops formed at the immunoglobulin heavy (IgH) chain are modified by ribose 2'-O-methylation (2'-OMe). Moreover, we find that 2'-O-methyltransferase fibrillarin (FBL) interacts with activation-induced cytidine deaminase (AID) associated snoRNA aSNORD1C to facilitate the 2'-OMe. Moreover, deleting AID C-terminal tail impairs its association with aSNORD1C and FBL. Disrupting FBL, AID or aSNORD1C expression severely impairs 2'-OMe, R-loop stability and CSR. Surprisingly, FBL, AID's interaction partner and aSNORD1C promoted AID targeting to the IgH locus.
Conclusion: Taken together, our results suggest that 2'-OMe stabilizes IgH-associated R-loops to enable productive CSR. These results would shed light on AID-mediated CSR and explain the mechanism of R-loop-associated genomic instability.
(© 2024. The Author(s).)
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معلومات مُعتمدة: CA130899 Republic of Korea National Cancer Center; CA132755 Republic of Korea National Cancer Center; R01 CA187209 United States CA NCI NIH HHS; P30 CA033572 United States CA NCI NIH HHS; CA187209 Republic of Korea National Cancer Center
فهرسة مساهمة: Keywords: 2'-O-methylation (2'-OMe); Activation-induced cytidine deaminase (AID); Class switching recombination (CSR); R-loop
المشرفين على المادة: EC 3.5.4.5 (Cytidine Deaminase)
EC 3.5.4.- (AICDA (activation-induced cytidine deaminase))
0 (Immunoglobulin Heavy Chains)
63231-63-0 (RNA)
تواريخ الأحداث: Date Created: 20240708 Date Completed: 20240709 Latest Revision: 20240802
رمز التحديث: 20240802
مُعرف محوري في PubMed: PMC11232215
DOI: 10.1186/s12915-024-01947-5
PMID: 38977974
قاعدة البيانات: MEDLINE
الوصف
تدمد:1741-7007
DOI:10.1186/s12915-024-01947-5