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

Abstract

Although BCL11b (B-cell lymphoma/leukemia 11B, CTIP2) is a well-known transcription repressor and tumor suppressor, its functions and cellular pathways are largely unknown. Here, we show that BCL11b interacts with RNA splicing/processing and nonsense-mediated decay (NMD) proteins, including FUS, SMN1, UPF1 and Drosha. Mass spectrometry analysis (LC-MS/MS) shows that BCL11b interacts with histones, polymerases, and chromatin remodeling (CHD, SWI/SNF, and topoisomerase) proteins. BCL11b-bound RNAs were UV cross-linked and sequenced (CLIP-seq) showing that BCL11b binds to coding and noncoding RNAs (ncRNAs). Surprisingly, RNA transcripts and proteins produced by the same genes like FUS, ESWR1, CHD and Tubulin, were found bound to BCL11b. Deeper analysis of the CLIP-seq data further suggested that BCL11b binds to nonsense mediated RNA decay and retained introns transcripts. Our study is the first genome-wide study of BCL11b-protein and BCL11b-RNA interactants. Our results suggest that the functions of BCL11b are not restricted to the regulation of gene transcription. BCL11b may also control physiologic and physiopathologic pathways by direct bindings to protein complexes, coding RNA and non-coding RNA.