核仁RNA聚合酶II促進核糖體生物發生
作者：
小柯機器人發布時間：2020/7/16 16:48:37
加拿大多倫多大學Karim Mekhail及其研究組發現核仁RNA聚合酶II促進核糖體形成。相關論文於2020年7月15日在線發表於《自然》雜誌。
在該研究中，研究人員發現人核仁中的RNA聚合酶II（Pol II）在編碼rRNA的基因附近誘導其表達。在神經退行性相關酶senataxin的輔助下，Pol II在核仁核糖體RNA（rRNA）基因兩側的基因間隔基上產生了一個包含三鏈核酸結構（稱為R環）的屏蔽。該屏蔽層可防止Pol I產生有義的基因間非編碼RNA（sincRNA），該RNA會破壞核仁組織和rRNA表達。這些破壞性sincRNA可以通過蛋白質RNaseH1、eGFP和dCas9的實驗系統（我們稱為「紅色雷射」）被Pol II抑制、senataxin喪失、尤因肉瘤或與基因座相關R環的阻抑而釋放出來。
該研究揭示了核仁Pol-II依賴的機制，其可促進核糖體生物發生，通過非編碼RNA識別疾病相關的核仁破壞，並建立針對基因座的R環調控。該發現修訂了主要RNA聚合酶之間分工的理論，並確定核仁Pol II是蛋白質合成和核組織的主要因子，對健康和疾病的研究具有潛在影響。
據了解，蛋白質是由核糖體翻譯產生的，核糖體是由蛋白質和RNA組成的大分子複合物，它們在核仁內組裝。現有模型表明，RNA聚合酶I和III（Pol I和Pol III）是唯一直接介導核糖體的組成成分rRNA表達的酶。
附：英文原文
Title: Nucleolar RNA polymerase II drives ribosome biogenesis
Author: Karan J. Abraham, Negin Khosraviani, Janet N. Y. Chan, Aparna Gorthi, Anas Samman, Dorothy Y. Zhao, Miling Wang, Michael Bokros, Elva Vidya, Lauren A. Ostrowski, Roxanne Oshidari, Violena Pietrobon, Parasvi S. Patel, Arash Algouneh, Rajat Singhania, Yupeng Liu, V. Talya Yerlici, Daniel D. De Carvalho, Michael Ohh, Brendan C. Dickson, Razq Hakem, Jack F. Greenblatt, Stephen Lee, Alexander J. R. Bishop, Karim Mekhail
Issue&Volume: 2020-07-15
Abstract: Proteins are manufactured by ribosomes—macromolecular complexes of protein and RNA molecules that are assembled within major nuclear compartments called nucleoli1,2. Existing models suggest that RNA polymerases I and III (Pol I and Pol III) are the only enzymes that directly mediate the expression of the ribosomal RNA (rRNA) components of ribosomes. Here we show, however, that RNA polymerase II (Pol II) inside human nucleoli operates near genes encoding rRNAs to drive their expression. Pol II, assisted by the neurodegeneration-associated enzyme senataxin, generates a shield comprising triplex nucleic acid structures known as R-loops at intergenic spacers flanking nucleolar rRNA genes. The shield prevents Pol I from producing sense intergenic noncoding RNAs (sincRNAs) that can disrupt nucleolar organization and rRNA expression. These disruptive sincRNAs can be unleashed by Pol II inhibition, senataxin loss, Ewing sarcoma or locus-associated R-loop repression through an experimental system involving the proteins RNaseH1, eGFP and dCas9 (which we refer to as 『red laser』). We reveal a nucleolar Pol-II-dependent mechanism that drives ribosome biogenesis, identify disease-associated disruption of nucleoli by noncoding RNAs, and establish locus-targeted R-loop modulation. Our findings revise theories of labour division between the major RNA polymerases, and identify nucleolar Pol II as a major factor in protein synthesis and nuclear organization, with potential implications for health and disease.
DOI: 10.1038/s41586-020-2497-0
Source: https://www.nature.com/articles/s41586-020-2497-0