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

BCL11b (B-cell lymphoma/leukemia 11B, CTIP2) is a C2H2 zinc-finger transcription regulator and tumor suppressor. BCL11b is involved in lymphomagenesis and in fetal, central nervous system (CNS) and immune system developments. Therefore, it may contribute in congenital disorders and cancers (e.g. leukemia). BCL11b favors persistence of HIV latency in microglia, CNS macrophages. BCL11b contributes to control cell cycle, differentiation and apoptosis in multiple organisms and cell models; however exact mechanisms are unknown. Although BCL11b recruits non-coding RNA and epigenetic enzymes to regulate gene expression, BCL11b-associated ribonucleoprotein complexes are unknown. Here, using immunoprecipitation of BCL11b-binding RNA and proteins (CLIP-seq and quantitative LC-MS/MS mass spectrometry) complemented with systems biology validations, we show that BCL11b interacts with RNA splicing and nonsense-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 First genome-wide BCL11b-protein and RNA interactome BCL11b interacts with RNA processing and splicing proteins BCL11b interacts with neurodegenerative genes and sarcoma genes BCL11b targets during cell proliferation and disease pathways ### Competing Interest Statement The authors have declared no competing interest.