snoRNA在核糖体小亚基组装中的作用

核糖体是由RNA和蛋白质组成的超大复合物，是地球上所有生物合成蛋白质的分子机器。在真核生物中，核糖体大小两个亚基的组装是个重要、保守和高度复杂的过程，出芽酵母需要200多个蛋白质因子和大量非编码小核仁snoRNA参与核糖体的组装。snoRNA分为H/ACA 和C/D两类，大部分snoRNA在核糖体RNA的修饰反应中提供底物特异性，但是U3、U14、snR30和snR10四条snoRNA在核糖体18S RNA的早期加工和小亚基组装起关键作用。和其他修饰snoRNA不同，U3、U14和snR30是酵母的必需基因，在所有真核生物中保守存在。本项目聚焦这四条snoRNA在酵母核糖体小亚基组装的作用，利用生物化学、遗传和结构生物学等手段，希望揭示早期小亚基90S前体在体内的组装过程，这四条snoRNA在90S形成中的作用，以及RNA解旋酶在snoRNA释放和90S的结构变化过程中的分子机制。

The ribosome is a large RNA protein complex that synthesizes protein in all organisms on our planet. Assembly of small and large ribosomal subunits is essential, conserved and highly complicated process in eukaryotes and requires more than 200 protein assembly factors and numerous non-coding snoRNAs in Saccharomyces cerevisiae. Majority of snoRNAs, which are classified into H/ACA and C/D types, function as guide in site-specific modification of rRNA, but U3, U14, snR30 and snR10 are special snoRNAs that are involved in early processing of 18S RNA and formation of small ribosomal subunit. Unlike other modification guide snoRNAs, U3, U14 and snR30 are essential for yeast growth and universally conserved in eukaryotes. This project focuses on the function of the four processing snoRNAs in assembly of small ribosomal subunit in yeast. Using biochemical, yeast genetic and structural approaches, we intend to dissect the assembly pathway of early small subunit 90S pre-ribosomes, the role of processing snoRNA in 90S formation and the role of RNA helicase in snoRNA release and structural reorganization of 90S pre-ribosomes.