MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development
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 mic...
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doaj-b7f3a2f5cb3d435990167d545422c4202021-07-15T04:27:28ZengElsevierCell Reports2211-12472021-07-01362109390MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell developmentRupa Kumari0Urbi Roy1Sagar Desai2Namrata M. Nilavar3Annemarie Van Nieuwenhuijze4Amita Paranjape5Gudapureddy Radha6Pushpinder Bawa7Mrinal Srivastava8Mridula Nambiar9Kithiganahalli Narayanaswamy Balaji10Adrian Liston11Bibha Choudhary12Sathees C. Raghavan13Department of Biochemistry, Indian Institute of Science, Bangalore 560012, IndiaDepartment of Biochemistry, Indian Institute of Science, Bangalore 560012, IndiaInstitute of Bioinformatics and Applied Biotechnology, Bangalore 560100, India; Manipal Academy of Higher Education, Manipal, Karnataka 576104, IndiaDepartment of Biochemistry, Indian Institute of Science, Bangalore 560012, IndiaDepartment of Microbiology and Immunology, Laboratory of Adaptive Immunity, KU Leuven, Leuven, BelgiumDepartment of Biochemistry, Indian Institute of Science, Bangalore 560012, IndiaDepartment of Biochemistry, Indian Institute of Science, Bangalore 560012, IndiaInstitute of Bioinformatics and Applied Biotechnology, Bangalore 560100, IndiaTIFR Centre for Interdisciplinary Sciences, Tata Institute of Fundamental Research (TIFR), Hyderabad 500046, IndiaDepartment of Biology, Indian Institute of Science Education and Research, Pune, IndiaDepartment of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, IndiaImmunology Programme, Babraham Institute, Cambridge, United KingdomInstitute of Bioinformatics and Applied Biotechnology, Bangalore 560100, India; Corresponding authorDepartment of Biochemistry, Indian Institute of Science, Bangalore 560012, India; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124721007889miRNARAG compleximmunoglobulin diversitylymphoid systemB cell developmentepigenetic regulation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rupa Kumari Urbi Roy Sagar Desai Namrata M. Nilavar Annemarie Van Nieuwenhuijze Amita Paranjape Gudapureddy Radha Pushpinder Bawa Mrinal Srivastava Mridula Nambiar Kithiganahalli Narayanaswamy Balaji Adrian Liston Bibha Choudhary Sathees C. Raghavan |
spellingShingle |
Rupa Kumari Urbi Roy Sagar Desai Namrata M. Nilavar Annemarie Van Nieuwenhuijze Amita Paranjape Gudapureddy Radha Pushpinder Bawa Mrinal Srivastava Mridula Nambiar Kithiganahalli Narayanaswamy Balaji Adrian Liston Bibha Choudhary Sathees C. Raghavan MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development Cell Reports miRNA RAG complex immunoglobulin diversity lymphoid system B cell development epigenetic regulation |
author_facet |
Rupa Kumari Urbi Roy Sagar Desai Namrata M. Nilavar Annemarie Van Nieuwenhuijze Amita Paranjape Gudapureddy Radha Pushpinder Bawa Mrinal Srivastava Mridula Nambiar Kithiganahalli Narayanaswamy Balaji Adrian Liston Bibha Choudhary Sathees C. Raghavan |
author_sort |
Rupa Kumari |
title |
MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development |
title_short |
MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development |
title_full |
MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development |
title_fullStr |
MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development |
title_full_unstemmed |
MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development |
title_sort |
microrna mir-29c regulates rag1 expression and modulates v(d)j recombination during b cell development |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2021-07-01 |
description |
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. |
topic |
miRNA RAG complex immunoglobulin diversity lymphoid system B cell development epigenetic regulation |
url |
http://www.sciencedirect.com/science/article/pii/S2211124721007889 |
work_keys_str_mv |
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