Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT.
Department of Cellular and Molecular Physiology, Yale University, New Haven, CT.
Mol Biol Evol. 2020 Jan 1;37(1):124-133. doi: 10.1093/molbev/msz207.
Eukaryotic cells are divided into the nucleus and the cytosol, and, to enter the nucleus, proteins typically possess short signal sequences, known as nuclear localization signals (NLSs). Although NLSs have long been considered as features unique to eukaryotic proteins, we show here that similar or identical protein segments are present in ribosomal proteins from the Archaea. Specifically, the ribosomal proteins uL3, uL15, uL18, and uS12 possess NLS-type motifs that are conserved across all major branches of the Archaea, including the most ancient groups Microarchaeota and Diapherotrites, pointing to the ancient origin of NLS-type motifs in the Archaea. Furthermore, by using fluorescence microscopy, we show that the archaeal NLS-type motifs can functionally substitute eukaryotic NLSs and direct the transport of ribosomal proteins into the nuclei of human cells. Collectively, these findings illustrate that the origin of NLSs preceded the origin of the cell nucleus, suggesting that the initial function of NLSs was not related to intracellular trafficking, but possibly was to improve recognition of nucleic acids by cellular proteins. Overall, our study reveals rare evolutionary intermediates among archaeal cells that can help elucidate the sequence of events that led to the origin of the eukaryotic cell.
真核细胞分为细胞核和细胞质，而蛋白质通常需要具有短的信号序列才能进入细胞核，这种短的信号序列被称为核定位信号（NLS）。尽管 NLS 长期以来一直被认为是真核蛋白质所特有的特征，但我们在这里表明，在古菌的核糖体蛋白中也存在类似或相同的蛋白质片段。具体来说，核糖体蛋白 uL3、uL15、uL18 和 uS12 具有 NLS 类型的基序，这些基序在古菌的所有主要分支中都保守存在，包括最古老的微古菌和 Diapherotrites 群，这表明 NLS 类型的基序在古菌中的起源非常古老。此外，通过使用荧光显微镜，我们表明这些古菌 NLS 类型的基序可以在功能上替代真核 NLS，并指导核糖体蛋白进入人类细胞的细胞核。总的来说，这些发现表明 NLS 的起源早于细胞核的起源，这表明 NLS 的最初功能与细胞内运输无关，而可能是改善细胞蛋白对核酸的识别。总的来说，我们的研究揭示了古菌细胞中罕见的进化中间体，这些中间体可以帮助阐明导致真核细胞起源的一系列事件。
