RNA processing mechanisms contribute to genome organization and stability in B cells

Abstract

AbstractRNA processing includes post-transcriptional mechanisms controlling RNA quality and quantity to ensure cellular homeostasis. Noncoding (nc) RNAs that are regulated by these dynamic processes may themselves fulfill effector and/or regulatory functions, and recent studies demonstrated the critical role of RNAs in organizing both chromatin and genome architectures. Furthermore, RNAs can threaten genome integrity when accumulating as DNA:RNA hybrids, but could also facilitate DNA repair depending on the molecular context. Therefore, by qualitatively and quantitatively fine-tuning RNAs, RNA processing contributes directly or indirectly to chromatin states, genome organization, and genome stability. B lymphocytes represent a unique model to study these interconnected mechanisms as they express ncRNAs transcribed from key specific sequences before undergoing physiological genetic remodeling processes, including V(D)J recombination, somatic hypermutation, and class switch recombination. RNA processing actors ensure the regulation and degradation of these ncRNAs for efficient DNA repair and immunoglobulin gene remodeling while failure leads to B cell development alterations, aberrant DNA repair, and pathological translocations. This review highlights how RNA processing mechanisms contribute to genome architecture and stability, with emphasis on their critical roles during B cell development, enabling physiological DNA remodeling while preventing lymphomagenesis.