Biomedical Sciences Ph.D. Program, Wright State University, Dayton, OH 45435, USA.
Masters of Biological Sciences Program, Wright State University, Dayton, OH 45435, USA.
Int J Mol Sci. 2017 Sep 12;18(9):1956. doi: 10.3390/ijms18091956.
Serine-arginine-rich (SR) or SR-like splicing factors interact with exon junction complex proteins during pre-mRNA processing to promote mRNA packaging into mature messenger ribonucleoproteins (mRNPs) and to dictate mRNA stability, nuclear export, and translation. The SR protein family is complex, and while many classical SR proteins have well-defined mRNA processing functions, those of other SR-like proteins is unclear. Here, we show that depletion of the homologous non-classical serine-arginine-rich (SR) splicing factors Bcl2-associated transcription factor (Btf or BCLAF) and thyroid hormone receptor-associated protein of 150 kDa (TRAP150) causes mitotic defects. We hypothesized that the depletion of these SR-like factors affects mitosis indirectly through an altered expression of mitotic checkpoint regulator transcripts. We observed an altered abundance of transcripts that encode mitotic regulators and mitotic chromosome misalignment defects following Btf and/or TRAP150 depletion. We propose that, in addition to their previously reported roles in maintaining mRNA distribution, Btf and TRAP150 control the abundance of transcripts encoding mitotic regulators, thereby affecting mitotic progression in human cells.
丝氨酸-精氨酸丰富（SR）或 SR 样剪接因子在 pre-mRNA 加工过程中与外显子结合复合体蛋白相互作用，以促进 mRNA 包装成成熟的信使核糖核蛋白（mRNPs），并决定 mRNA 的稳定性、核输出和翻译。SR 蛋白家族很复杂，虽然许多经典的 SR 蛋白具有明确的 mRNA 处理功能，但其他 SR 样蛋白的功能尚不清楚。在这里，我们表明同源的非经典丝氨酸-精氨酸丰富（SR）剪接因子 Bcl2 相关转录因子（Btf 或 BCLAF）和 150 kDa 甲状腺激素受体相关蛋白（TRAP150）的耗竭会导致有丝分裂缺陷。我们假设这些 SR 样因子的耗竭通过改变有丝分裂检查点调节剂转录本的表达间接影响有丝分裂。我们观察到 Btf 和/或 TRAP150 耗竭后，编码有丝分裂调节剂的转录本的丰度发生改变，并且有丝分裂染色体错位缺陷。我们提出，除了它们在维持 mRNA 分布方面的先前报道的作用外，Btf 和 TRAP150 还控制编码有丝分裂调节剂的转录本的丰度，从而影响人类细胞的有丝分裂进程。
