Deragon Jean-Marc, Bousquet-Antonelli Cécile
CNRS, LGDP-UMR5096, Perpignan, France.
University of Perpignan, LGDP-UMR5096, Perpignan, France.
Wiley Interdiscip Rev RNA. 2015 Jul-Aug;6(4):399-417. doi: 10.1002/wrna.1282. Epub 2015 Apr 17.
The LARP1 proteins form an evolutionarily homogeneous subgroup of the eukaryotic superfamily of La-Motif (LAM) containing factors. Members of the LARP1 family are found in most protists, fungi, plants, and animals. We review here evidence suggesting that LARP1 are key versatile messenger RNA (mRNA)-binding proteins involved in regulating important biological processes such as gametogenesis, embryogenesis, sex determination, and cell division in animals, as well as acclimation to stress in yeasts and plants. LARP1 proteins perform all these essential tasks likely by binding to key mRNAs and regulating their stability and/or translation. In human, the impact of LARP1 over cell division and proliferation is potentially under the control of the TORC1 complex. We review data suggesting that LARP1 is a direct target of this master signaling hub. TOR-dependent LARP1 phosphorylation could specifically enhance the translation of TOP mRNAs providing a way to promote translation, growth, and proliferation. Consequently, LARP1 is found to be significantly upregulated in many malignant cell types. In plants, LARP1 was found to act as a cofactor of the heat-induced mRNA degradation process, an essential acclimation strategy leading to the degradation of more than 4500 mRNAs coding for growth and development housekeeping functions. In Saccharomyces cerevisiae, the LARP1 proteins (Slf1p and Sro9p) are important, among other things, for copper resistance and oxidative stress survival. LARP1 proteins are therefore emerging as critical ancient mRNA-binding factors that evolved common as well as specific targets and regulatory functions in all eukaryotic lineages.
LARP1蛋白形成了含La基序（LAM）因子的真核超家族中一个进化上同源的亚组。LARP1家族成员存在于大多数原生生物、真菌、植物和动物中。我们在此综述相关证据，表明LARP1是关键的多功能信使核糖核酸（mRNA）结合蛋白，参与调控重要的生物学过程，如动物的配子发生、胚胎发生、性别决定和细胞分裂，以及酵母和植物对胁迫的适应。LARP1蛋白可能通过与关键mRNA结合并调节其稳定性和/或翻译来执行所有这些重要任务。在人类中，LARP1对细胞分裂和增殖的影响可能受TORC1复合体的控制。我们综述的数据表明LARP1是这个主要信号枢纽的直接靶点。TOR依赖的LARP1磷酸化可特异性增强TOP mRNA的翻译，为促进翻译、生长和增殖提供一种途径。因此，在许多恶性细胞类型中发现LARP1显著上调。在植物中，LARP1被发现是热诱导mRNA降解过程的一个辅助因子，这是一种重要的适应策略，导致4500多种编码生长和发育管家功能的mRNA降解。在酿酒酵母中，LARP1蛋白（Slf1p和Sro9p）除其他作用外，对铜抗性和氧化应激存活很重要。因此，LARP1蛋白正成为关键的古老mRNA结合因子，在所有真核生物谱系中进化出了共同以及特定的靶点和调控功能。
