Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States.
Medical Scientist Training Program, University of Texas Southwestern Medical Center, Dallas, United States.
Elife. 2019 Jul 25;8:e48625. doi: 10.7554/eLife.48625.
is a conserved long noncoding RNA (lncRNA) that is required for genome stability in mammals. acts as a negative regulator of PUMILIO (PUM) proteins in the cytoplasm, and we previously showed that loss of or PUM hyperactivity results in genome instability and premature aging in mice (Kopp et al., 2019). Recently, however, it was reported that regulates genome stability through an interaction with the RNA binding protein RBMX in the nucleus. Here, we addressed the contributions of :PUM and :RBMX interactions to genome maintenance by this lncRNA in human cells. Extensive RNA FISH and fractionation experiments established that localizes predominantly to the cytoplasm with or without DNA damage. Moreover, genetic rescue experiments demonstrated that PUM binding is required for maintenance of genomic stability by whereas binding of RBMX is dispensable for this function. These data provide an important foundation for further mechanistic dissection of the -PUMILIO axis in genome maintenance.
是一种保守的长非编码 RNA（lncRNA），对于哺乳动物的基因组稳定性至关重要。 在细胞质中作为 PUMILIO（PUM）蛋白的负调控因子发挥作用，我们之前的研究表明， 的缺失或 PUM 的过度活跃会导致小鼠的基因组不稳定性和过早衰老（Kopp 等人，2019）。然而，最近有报道称， 通过与核内 RNA 结合蛋白 RBMX 的相互作用来调节基因组稳定性。在这里，我们通过该 lncRNA 在人类细胞中研究了 :PUM 和 :RBMX 相互作用对基因组维持的贡献。广泛的 RNA FISH 和分级实验确立了 无论有无 DNA 损伤，主要定位于细胞质。此外，遗传挽救实验表明，PUM 结合对于 通过 维持基因组稳定性是必需的，而 RBMX 的结合对于该功能是可有可无的。这些数据为进一步深入研究基因组维持中的 -PUMILIO 轴的机制提供了重要基础。
