Abstract
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.
Overview
- The study investigates the role of BCL11b in lymphomagenesis, central nervous system (CNS) and immune system developments. It also explores the interaction of BCL11b 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). The study highlights that BCL11b targets RNA processing and splicing proteins, and RNAs that implicate cell cycle, development, neurodegenerative, and cancer pathways. The primary objective of the study is to understand the mechanisms underlying BCL11b's role in these pathways and its interaction with RNA processing and splicing proteins.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The results 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). The study also highlights that BCL11b targets RNA processing and splicing proteins, and RNAs that implicate cell cycle, development, neurodegenerative, and cancer pathways. The key findings of the study suggest that BCL11b plays a crucial role in RNA processing and splicing, and its interaction with specific nucleoprotein complexes involved in the regulation of genes expression.
Implications and Future Directions
- The study's findings have significant implications for the field of research and clinical practice. The study reveals BCL11b's association with specific nucleoprotein complexes involved in the regulation of genes expression, which may have implications for the development of new therapies for developmental disorders. The study also highlights the importance of RNA processing and splicing in cell cycle, development, neurodegenerative, and cancer pathways. Future research directions could build on the results of the study, explore unresolved questions, or utilize novel approaches to further understand the mechanisms underlying BCL11b's role in these pathways and its interaction with RNA processing and splicing proteins.