Abstract：
Microdeletion of the 15q11.2 BP1-BP2 region, also known as Burnside-Butler susceptibility region, is associated with phenotypes like delayed developmental language abilities along with motor skill disabilities, combined with behavioral and emotional problems. The 15q11.2 microdeletion region harbors four evolutionarily conserved and non-imprinted protein-coding genes: NIPA1, NIPA2, CYFIP1, and TUBGCP5. This microdeletion is a rare copy number variation frequently associated with several pathogenic conditions in humans. The aim of this study is to investigate the RNA-binding proteins binding with the four genes present in 15q11.2 BP1-BP2 microdeletion region. The results of this study will help to better understand the molecular intricacies of the Burnside-Butler Syndrome and also the possible involvement of these interactions in the disease aetiology. Our results of enhanced crosslinking and immunoprecipitation data analysis indicate that most of the RBPs interacting with the 15q11.2 region are involved in the post-transcriptional regulation of the concerned genes. The RBPs binding to this region are found from the in silico analysis, and the interaction of RBPs like FASTKD2 and EFTUD2 with exon-intron junction sequence of CYFIP1 and TUBGCP5 has also been validated by combined EMSA and western blotting experiment. The exon-intron junction binding nature of these proteins suggests their potential involvement in splicing process. This study may help to understand the intricate relationship of RBPs with mRNAs within this region, along with their functional significance in normal development, and lack thereof, in neurodevelopmental disorders. This understanding will help in the formulation of better therapeutic approaches.
摘要：
15q11.2BP1-BP2区域的微缺失，也被称为伯恩赛德-巴特勒敏感区，与发育迟缓的语言能力和运动技能障碍等表型相关，结合行为和情绪问题。15q11.2微缺失区包含四个进化保守和非印迹蛋白编码基因：NIPA1，NIPA2，CYFIP1和TUBGCP5。这种微缺失是一种罕见的拷贝数变异，通常与人类的几种致病状况有关。这项研究的目的是研究与15q11.2BP1-BP2微缺失区中存在的四个基因结合的RNA结合蛋白。这项研究的结果将有助于更好地了解Burnside-Butler综合征的分子复杂性，以及这些相互作用在疾病病因中的可能参与。我们的增强交联和免疫沉淀数据分析结果表明，与15q11.2区域相互作用的大多数RBP都参与相关基因的转录后调控。通过计算机模拟分析发现与该区域结合的RBP，并且通过EMSA和Western印迹联合实验也验证了RBP如FASTKD2和EFTUD2与CYFIP1和TUBGCP5的外显子-内含子连接序列的相互作用。这些蛋白质的外显子-内含子连接结合性质表明它们可能参与剪接过程。这项研究可能有助于理解RBPs与该区域内mRNA的复杂关系，以及它们在正常发育中的功能意义，和缺乏，神经发育障碍。这种理解将有助于制定更好的治疗方法。
