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

• DOI: 10.1016/j.celrep.2021.109390
• Publication Date: 2021-07-13T15:12:57Z
• Authors: Rupa Kumari; Urbi Roy; Sagar Desai; Namrata M. Nilavar; Annemarie Van Nie...; Amita Paranjape; Gudapureddy Radha; Pushpinder Bawa; Mrinal Srivastava; Mridula Nambiar; Kithiganahalli Na...; Adrian Liston; Bibha Choudhary; Sathees C. Raghavan
• Keywords: 0301 basic medicine; PROMOTER; QH301-705.5; ACUTE MYELOID-LEUKEMIA; epigenetic regulation; C-MYB; 03 medical and health sciences; ACTIVATING GENES; Cell Line, Tumor; B cell development; lymphoid system; Animals; Humans; Lymphocytes; Biology (General); RNA Processing, Post-Transcriptional; Luciferases; 3' Untranslated Regions; miRNA; Homeodomain Proteins; immunoglobulin diversity; B-Lymphocytes; Mice, Inbred BALB C; Science & Technology; IDENTIFICATION; Base Sequence; Cell Biology; DNA; MAJOR BREAKPOINT REGION; CANCER; V(D)J Recombination; FAMILY; TRANSLOCATION; 3. Good health; Mice, Inbred C57BL; MicroRNAs; Gene Expression Regulation; RAG complex; CRISPR-Cas Systems; Life Sciences & Biomedicine

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 through a microRNA (miRNA), miR-29c, B cell stage-specific manner mice humans. Various lines experimentation, including CRISPR-Cas9 genome editing, demonstrate target specificity direct interaction miR-29c to RAG1. Modulation levels leads change efficiency pre-B cells. The expression is inversely proportional developmental manner, null exhibit reduction mature A negative correlation also observed leukemia patients, suggesting potential use as biomarker therapeutic target. Thus, our results reveal role miRNA its relevance cancer.