Control of RNA processing during RNA polymerase II transcription

细胞必须将DNA中编码的信息转化为蛋白质编码信使（m）RNA或调节性非编码（nc）RNA，这是通过RNA聚合酶II（Pol II）转录过程实现的。在Pol II转录过程中，真核RNA前体被加工成其成熟的功能形式。RNA加工调节的缺陷与神经退行性疾病和癌症有关。虽然Pol II转录在RNA加工调控中的重要性已得到充分证实，但其潜在的分子机制仍知之甚少。基于我们最近的发现，我们提出与转录Pol II相关的转录因子通过在转录期间调节RNA加工酶的活性来介导RNA加工。本研究旨在揭示基因表达的调控机制、相关因子及其对基因表达的作用，以验证我们的假设。这项工作产生的机制见解将揭示管理基因调控的普遍原则，告知转录失调如何导致人类疾病，并在长期指导未来治疗方法的发展，提高靶向的特异性。

Cells must convert information encoded in DNA into protein-coding messenger (m)RNA or regulatory non-coding (nc)RNAs, which is achieved through a process of RNA polymerase II (Pol II) transcription. During Pol II transcription eukaryotic RNA precursors are processed into their mature functional form. Defects in regulation of RNA processing are associated with neurodegenerative disorders and cancer. Although importance of Pol II transcription in regulation of RNA processing is well established, the underlying molecular mechanisms are poorly understood. Building upon our recent discoveries, we propose that transcription factors associated with the transcribing Pol II, mediate RNA processing by regulating activity of the RNA processing enzymes during transcription. This proposal aims to uncover underlying regulatory mechanisms, factors involved and their functional contribution to gene expression to test our hypothesis. The mechanistic insight generated by this work will uncover universal principles that govern gene regulation, inform on how dysregulated transcription could lead to human disease and in the long term guide development of future therapeutic approaches with improved specificity of targeting.