Nat Commun:中山大學高嵩課題組和謝偉教授課題組合作揭示真核生物的翻譯調控機制
2018年3月21日,國際學術權威刊物自然出版集團旗下子刊《Nature Communication》雜誌線上發表了中山大學附屬腫瘤醫院高嵩研究員課題組和生科院謝偉教授課題組合作的一篇研究論文,論文報導了Schlafen(SLFN)蛋白家族被發現20年以來的第一個晶體結構,
細胞在受到外界不良環境刺激(包括饑餓、氧化壓力、腫瘤脅迫和病毒感染等)時,通過酶切細胞內的tRNA/rRNA調控翻譯過程來控制細胞代謝是保守又高效的關鍵策略,可以幫助細胞快速釋放壓力以度過難關。病毒和腫瘤往往是細胞最難以招架的刺激性因素,對人類的健康造成嚴重威脅。然而,在包括人類在內的高等真核生物中,
SLFN是一個功能多樣的多成員蛋白家族,所有成員均含有一個保守且獨特的N端結構域,與其它已知蛋白的序列相似性有限,
這項研究成果為SLFN家族的後續研究和應用奠定了基礎,並為開發相關的病毒抑制手段和腫瘤防治策略提供了新思路。
SLFN13-N的結構和作用機制模型
原文連結:
原文摘要:
Cleavage of transfer (t)RNA and ribosomal (r)RNA are critical and conserved steps of translational control for cells to overcome varied environmental stresses. However, enzymes that are responsible for this event have not been fully identified in high eukaryotes. Here, we report a mammalian tRNA/rRNA-targeting endoribonuclease: SLFN13, a member of the Schlafen family. Structural study reveals a unique pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N′-domain that may clamp base-paired RNAs. SLFN13 is able to digest tRNAs and rRNAs in vitro, and the endonucleolytic cleavage dissevers 11 nucleotides from the 3′-terminus of tRNA at the acceptor stem. The cytoplasmically localised SLFN13 inhibits protein synthesis in 293T cells. Moreover, SLFN13 restricts HIV replication in a nucleolytic activity-dependent manner. According to these observations, we term SLFN13 RNase S13. Our study provides insights into the modulation of translational machinery in high eukaryotes, and sheds light on the functional mechanisms of the Schlafen family.