MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development

Cell Reports

Namrata M. Nilavar¹  Urbi Roy²  Gudapureddy Radha²  Annemarie Van Nieuwenhuijze²  Pushpinder Bawa²  Rupa Kumari²  Kithiganahalli Narayanaswamy Balaji³  Adrian Liston⁴  Amita Paranjape⁵  Bibha Choudhary⁶  Sagar Desai⁷  Sathees C. Raghavan⁷  Mrinal Srivastava⁷  Mridula Nambiar⁸ 

[1] Manipal Academy of Higher Education, Manipal, Karnataka 576104, India;Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India;Department of Biology, Indian Institute of Science Education and Research, Pune, India;Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India;Department of Microbiology and Immunology, Laboratory of Adaptive Immunity, KU Leuven, Leuven, Belgium;Immunology Programme, Babraham Institute, Cambridge, United Kingdom;Institute of Bioinformatics and Applied Biotechnology, Bangalore 560100, India;TIFR Centre for Interdisciplinary Sciences, Tata Institute of Fundamental Research (TIFR), Hyderabad 500046, India;

关键词: miRNA;    RAG complex;    immunoglobulin diversity;    lymphoid system;    B cell development;    epigenetic regulation;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Recombination activating genes (RAGs), consisting of RAG1 and RAG2, are stringently regulated lymphoid-specific genes, which initiate V(D)J recombination in developing lymphocytes. We report the regulation of RAG1 through a microRNA (miRNA), miR-29c, in a B cell stage-specific manner in mice and humans. Various lines of experimentation, including CRISPR-Cas9 genome editing, demonstrate the target specificity and direct interaction of miR-29c to RAG1. Modulation of miR-29c levels leads to change in V(D)J recombination efficiency in pre-B cells. The miR-29c expression is inversely proportional to RAG1 in a B cell developmental stage-specific manner, and miR-29c null mice exhibit a reduction in mature B cells. A negative correlation of miR-29c and RAG1 levels is also observed in leukemia patients, suggesting the potential use of miR-29c as a biomarker and a therapeutic target. Thus, our results reveal the role of miRNA in the regulation of RAG1 and its relevance in cancer.

【 授权许可】

Unknown