RNA motifs：核醣體演化的轉捩點

Abstract

核醣體是所有生命體中不可或缺的蛋白質轉譯的工廠。核醣體的基本結構包含了重複性的核醣核酸二級結構，又稱作模體(motifs)，像是A-helix, tetraloop, kink-turn, E-loop等。核醣核酸模體被認為具有：(1)啟動及輔助核醣核酸的折疊，(2)提供辨識的平台以形成三級結構，(3)穩定核醣核酸分子的複合體。近年來，在單一粒子冷凍電子顯微鏡的輔助下，一些非常複雜的真核生物的核醣體結構，像是智人80S的核醣體，得以在接近原子層級的解析度下被解析出來。智人的60S核醣體中的大次單元中包含了28S、5.8S、5S核醣體核醣核酸和47個核醣體蛋白質，並且擁有著比細菌及古菌的50S核醣體多出了21個值得注意的擴張片段(expansion segments)。 在這篇論文中，我們利用結構探勘去針對智人60S核醣體中的tetraloop, kink-turn, E-loop三種核醣核酸模體進行重複的搜尋。到目前為止，我們總共在智人的28S核醣體核醣核酸中鑑定並驗證出59組核醣核酸模體(33組tetraloops,20組kink-turns,6組E-loops)。接著，藉由核醣體洋蔥模型(onion model)，我們發現智人的28S核醣核酸模體會和核醣體的大次單元共同演化。另外，從古生菌到真核生物的4種物種的核醣體的交叉比較分析中，顯示出核醣核酸模體極有可能是智人核醣體的大次單元中的擴張片段所坐落的位置。

Ribosome, the machinery of translation, is essential in all living organisms. The fundamental architecture of the ribosome consists of repetitive RNA secondary structures, including A-helix, tetraloop, kink-turn, E-loop, etc., which are so-called motifs. The RNA motifs are thought to (i) initiate and facilitate the RNA folding, (ii) provide recognition platforms to form tertiary structures, and (iii) stabilize complex RNA molecules. Recently, some very complicated structures of the eukaryotic ribosomes, for example, the Homo sapiens 80S ribosome, are revealed at near-atomic resolution in the assist of single-particle cryo-electron microscopy. The large subunit of the H. sapiens 60S ribosome, which consists of 28S, 5.8S, and 5S rRNAs and 47 ribosomal proteins, has notable 21 rRNA expansion segments, compared to that of bacterial and archaeal 50S ribosomes. Here we perform the structural mining to recursively search for RNA motifs, including tetraloops, kink-turns, and E-loops within the H. sapiens 60S ribosome. By far, a total of 59 RNA motifs from the H. sapiens 28S rRNA (33 tetraloops; 20 kink-turns; 6 E-loops) are identified and verified. By using the onion model of the ribosome, the H. sapiens 28S rRNA motifs are shown to be adaptively co-evolved with the large subunit of the ribosome. In addition, the cross-comparison analysis on structures of the four species ribosomes from Archaea and Eukarya, indicates that RNA motifs are plausible sites for expansion segments in the large subunit of the H. sapiens 60S ribosome.