ABSTRACT

La and La-related proteins (LARPs) are characterized by a common RNA interaction platform termed the La module. This structural hallmark allows LARPs to pervade various aspects of RNA biology. The metazoan LARP7 protein binds to the 7SK RNA as part of a 7SK small nuclear ribonucleoprotein (7SK snRNP), which inhibits the transcriptional activity of RNA polymerase II (Pol II). Additionally, recent findings revealed unanticipated roles of LARP7 in the assembly of other RNPs, as well as in the modification, processing and cellular transport of RNA molecules. Reduced levels of functional LARP7 have been linked to cancer and Alazami syndrome, two seemingly unrelated human diseases characterized either by hyperproliferation or growth retardation. Here, we review the intricate regulatory networks centered on LARP7 and assess how malfunction of these networks may relate to the etiology of LARP7-linked diseases.

摘要

La 和 La 相关蛋白 (LARP) 的特征在于称为 La 模块的常见 RNA 相互作用平台。这种结构标志使 LARP 能够渗透到 RNA 生物学的各个方面。后生动物 LARP7 蛋白与 7SK RNA 结合，作为 7SK 小核核糖核蛋白 (7SK snRNP) 的一部分，抑制 RNA 聚合酶 II (Pol II) 的转录活性。此外，最近的研究结果揭示了 LARP7 在其他 RNP 的组装以及 RNA 分子的修饰、加工和细胞转运中的意外作用。功能性 LARP7 水平降低与癌症和阿拉扎米综合征有关，这两种看似无关的人类疾病的特征是过度增殖或生长迟缓。这里，