Mitochondria-associated RNA-binding proteins (RBPs) have emerged as key contributors to mitochondrial biogenesis and homeostasis. With few examples known, we set out to identify RBPs that regulate nuclear-encoded mitochondrial mRNAs (NEMmRNAs). Our systematic analysis of RNA targets of 150 RBPs identified RBPs with a preference for binding NEMmRNAs, including LARP4, a La RBP family member. We show that LARP4's targets are particularly enriched in mRNAs that encode respiratory chain complex proteins (RCCPs) and mitochondrial ribosome proteins (MRPs) across multiple human cell lines. Through quantitative proteomics, we demonstrate that depletion of LARP4 leads to a significant reduction in RCCP and MRP protein levels. Furthermore, we show that LARP4 depletion reduces mitochondrial function, and that LARP4 re-expression rescues this phenotype. Our findings shed light on a novel function for LARP4 as an RBP that binds to and positively regulates NEMmRNAs to promote mitochondrial respiratory function.

中文翻译：

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LARP4 是一种 RNA 结合蛋白，可结合核编码的线粒体 mRNA 以促进线粒体功能

线粒体相关 RNA 结合蛋白 (RBP) 已成为线粒体生物发生和稳态的关键贡献者。由于已知的例子很少，我们着手鉴定调节核编码线粒体 mRNA (NEMmRNA) 的 RBP。我们对 150 个 RBP 的 RNA 靶标进行系统分析，确定了优先结合 NEMmRNA 的 RBP，包括 La RBP 家族成员 LARP4。我们发现，LARP4 的靶标特别富含编码多种人类细胞系呼吸链复合蛋白 (RCCP) 和线粒体核糖体蛋白 (MRP) 的 mRNA。通过定量蛋白质组学，我们证明 LARP4 的消耗会导致 RCCP 和 MRP 蛋白水平显着降低。此外，我们发现 LARP4 缺失会降低线粒体功能，而 LARP4 重新表达可以挽救这种表型。我们的研究结果揭示了 LARP4 作为 RBP 的一种新功能，它与 NEMmRNA 结合并积极调节 NEMmRNA 以促进线粒体呼吸功能。