MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development
| Autor: | Urbi Roy, Mridula Nambiar, Annemarie van Nieuwenhuijze, Mrinal Srivastava, Pushpinder Singh Bawa, Adrian Liston, Bibha Choudhary, Sathees C. Raghavan, Sagar S. Desai, Amita M Paranjape, Rupa Kumari, Gudapureddy Radha, Namrata M Nilavar, Kithiganahalli Narayanaswamy Balaji |
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| Rok vydání: | 2021 |
| Předmět: |
PROMOTER
Genome editing hemic and lymphatic diseases B cell development Lymphocytes RNA Processing Post-Transcriptional Biology (General) Luciferases 3' Untranslated Regions B-Lymphocytes Mice Inbred BALB C immunoglobulin diversity Chemistry V(D)J recombination hemic and immune systems MAJOR BREAKPOINT REGION CANCER FAMILY TRANSLOCATION Cell biology medicine.anatomical_structure Life Sciences & Biomedicine QH301-705.5 chemical and pharmacologic phenomena ACUTE MYELOID-LEUKEMIA epigenetic regulation General Biochemistry Genetics and Molecular Biology Recombination-activating gene C-MYB ACTIVATING GENES RAG2 Cell Line Tumor microRNA lymphoid system medicine Animals Humans Epigenetics Gene B cell miRNA Homeodomain Proteins Science & Technology Base Sequence IDENTIFICATION Cell Biology DNA V(D)J Recombination Mice Inbred C57BL MicroRNAs Gene Expression Regulation RAG complex CRISPR-Cas Systems |
| Zdroj: | Cell Reports, Vol 36, Iss 2, Pp 109390-(2021) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2021.109390 |
| Popis: | 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. ispartof: CELL REPORTS vol:36 issue:2 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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