RNA 聚合酶-I (Pol I) 轉(zhuǎn)錄核糖體RNA(后者是核糖體組裝必不可少的),,因此這種酶是蛋白生物合成和細(xì)胞生長的一個(gè)主要決定因子,。
Pol I的誤調(diào)控已被與幾種類型的癌癥聯(lián)系了起來,而且Pol I也在成為抗癌藥物的一個(gè)目標(biāo),。
在本期Nature上,,獨(dú)立工作的兩個(gè)小組發(fā)表了分別以3.0 A 和 2.8 A分辨率確定的由14個(gè)亞單元組成的酵母完整Pol I的X-射線晶體結(jié)構(gòu)。
Pol I的基本結(jié)構(gòu)與Pol II 和 Pol III的基本結(jié)構(gòu)相似,,但其DNA結(jié)合槽有一個(gè)比在其他RNA聚合酶中所見到的更寬的構(gòu)形,,同時(shí)其他特點(diǎn)也讓我們對其不同組成部分的功能角色有所認(rèn)識。(生物谷Bioon.com)
生物谷推薦的英文摘要
Nature doi:10.1038/nature12636
Crystal structure of the 14-subunit RNA polymerase I
Carlos Fernandez-Tornero,,Maria Moreno-Morcillo,,Umar J. Rashid,Nicholas M. I. Taylor,,F(xiàn)ederico M. Ruiz,,Tim Gruene,Pierre Legrand,,Ulrich Steuerwald& Christoph W. Müller
Protein biosynthesis depends on the availability of ribosomes,, which in turn relies on ribosomal RNA production. In eukaryotes, this process is carried out by RNA polymerase I (Pol I),, a 14-subunit enzyme,, the activity of which is a major determinant of cell growth. Here we present the crystal structure of Pol I from Saccharomyces cerevisiae at 3.0 resolution. The Pol I structure shows a compact core with a wide DNA-binding cleft and a tightly anchored stalk. An extended loop mimics the DNA backbone in the cleft and may be involved in regulating Pol I transcription. Subunit A12.2 extends from the A190 jaw to the active site and inserts a transcription elongation factor TFIIS-like zinc ribbon into the nucleotide triphosphate entry pore, providing insight into the role of A12.2 in RNA cleavage and Pol I insensitivity to α-amanitin. The A49–A34.5 heterodimer embraces subunit A135 through extended arms,, thereby contacting and potentially regulating subunit A12.2.
doi:10.1038/nature12712
RNA polymerase I structure and transcription regulation
Christoph EngelSarah SainsburyAlan C. CheungDirk KostrewaPatrick Cramer
Transcription of ribosomal RNA by RNA polymerase (Pol) I initiates ribosome biogenesis and regulates eukaryotic cell growth. The crystal structure of Pol I from the yeast Saccharomyces cerevisiae at 2.8 resolution reveals all 14subunits of the 590-kilodalton enzyme,, and shows differences to Pol II. An ‘expander’ element occupies the DNA template site and stabilizes an expanded active centre cleft with an unwound bridge helix. A ‘connector’ element invades the cleft of an adjacent polymerase and stabilizes an inactive polymerase dimer. The connector and expander must detach during Pol I activation to enable transcription initiation and cleft contraction by convergent movement of the polymerase ‘core’ and ‘shelf’ modules. Conversion between an inactive expanded and an active contracted polymerase state may generally underlie transcription. Regulatory factors can modulate the core–shelf interface that includes a ‘composite’ active site for RNA chain initiation, elongation,, proofreading and termination.