BCL11b interacts with RNA and proteins involved in RNA processing and developmental diseases

BCL11b is a transcription regulator and a tumor suppressor involved in lymphomagenesis, central nervous system (CNS) and immune system developments. BCL11b favors persistence of HIV latency and contributes to control cell cycle, differentiation and apoptosis in multiple organisms and cell models. Although BCL11b recruits the non-coding RNA 7SK and epigenetic enzymes to regulate gene expression, BCL11b-associated ribonucleoprotein complexes are unknown. Thanks to CLIP-seq and quantitative LC-MS/MS mass spectrometry approaches complemented with systems biology validations, we show that BCL11b interacts with RNA splicing and non-sense-mediated decay proteins, including FUS, SMN1, UPF1 and Drosha, which may contribute in isoform selection of protein-coding RNA isoforms from noncoding-RNAs isoforms (retained introns or nonsense mediated RNA). Interestingly, BCL11b binds to RNA transcripts and proteins encoded by the same genes (FUS, ESWR1, CHD and Tubulin). Our study highlights that BCL11b targets RNA processing and splicing proteins, and RNAs that implicate cell cycle, development, neurodegenerative, and cancer pathways. These findings will help future mechanistic understanding of developmental disorders. IMPORTANCE: BCL11b-protein and RNA interactomes reveal BLC11b association with specific nucleoprotein complexes involved in the regulation of genes expression. BCL11b interacts with RNA processing and splicing proteins.