Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
Nucleic Acids Res. 2012 Feb;40(3):1381-94. doi: 10.1093/nar/gkr890. Epub 2011 Oct 18.
Human La protein is an essential factor in the biology of both coding and non-coding RNAs. In the nucleus, La binds primarily to 3' oligoU containing RNAs, while in the cytoplasm La interacts with an array of different mRNAs lacking a 3' UUU(OH) trailer. An example of the latter is the binding of La to the IRES domain IV of the hepatitis C virus (HCV) RNA, which is associated with viral translation stimulation. By systematic biophysical investigations, we have found that La binds to domain IV using an RNA recognition that is quite distinct from its mode of binding to RNAs with a 3' UUU(OH) trailer: although the La motif and first RNA recognition motif (RRM1) are sufficient for high-affinity binding to 3' oligoU, recognition of HCV domain IV requires the La motif and RRM1 to work in concert with the atypical RRM2 which has not previously been shown to have a significant role in RNA binding. This new mode of binding does not appear sequence specific, but recognizes structural features of the RNA, in particular a double-stranded stem flanked by single-stranded extensions. These findings pave the way for a better understanding of the role of La in viral translation initiation.
人类 La 蛋白是编码和非编码 RNA 生物学的重要因素。在核内，La 主要与含有 3' 寡聚 U 的 RNA 结合，而在细胞质中，La 与一系列缺乏 3' UUU(OH) 尾部的不同 mRNA 相互作用。后者的一个例子是 La 与丙型肝炎病毒 (HCV) RNA 的 IRES 结构域 IV 的结合，这与病毒翻译的刺激有关。通过系统的生物物理研究，我们发现 La 与 IV 结构域的结合使用的 RNA 识别方式与与 3' UUU(OH) 尾部的 RNA 结合的方式截然不同：尽管 La 基序和第一个 RNA 识别基序 (RRM1) 足以与 3' 寡聚 U 高亲和力结合，但 HCV 结构域 IV 的识别需要 La 基序和 RRM1 与以前未显示在 RNA 结合中具有重要作用的非典型 RRM2 协同作用。这种新的结合模式似乎不是序列特异性的，而是识别 RNA 的结构特征，特别是由单链延伸侧翼的双链茎。这些发现为更好地理解 La 在病毒翻译起始中的作用铺平了道路。
