Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Fukuoka, 812-8582, Japan.
Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, 812-8582, Japan.
Nat Commun. 2023 Apr 20;14(1):2131. doi: 10.1038/s41467-023-37838-6.
Although several ribosomal protein paralogs are expressed in a tissue-specific manner, how these proteins affect translation and why they are required only in certain tissues have remained unclear. Here we show that RPL3L, a paralog of RPL3 specifically expressed in heart and skeletal muscle, influences translation elongation dynamics. Deficiency of RPL3L-containing ribosomes in RPL3L knockout male mice resulted in impaired cardiac contractility. Ribosome occupancy at mRNA codons was found to be altered in the RPL3L-deficient heart, and the changes were negatively correlated with those observed in myoblasts overexpressing RPL3L. RPL3L-containing ribosomes were less prone to collisions compared with RPL3-containing canonical ribosomes. Although the loss of RPL3L-containing ribosomes altered translation elongation dynamics for the entire transcriptome, its effects were most pronounced for transcripts related to cardiac muscle contraction and dilated cardiomyopathy, with the abundance of the encoded proteins being correspondingly decreased. Our results provide further insight into the mechanisms and physiological relevance of tissue-specific translational regulation.
虽然有几种核糖体蛋白的同工蛋白以组织特异性的方式表达，但这些蛋白如何影响翻译以及为什么它们只在某些组织中需要，这些问题仍不清楚。在这里，我们表明 RPL3L，一种在心脏和骨骼肌中特异性表达的 RPL3 同工蛋白，影响翻译延伸动力学。RPL3L 敲除雄性小鼠中缺乏含有 RPL3L 的核糖体导致心脏收缩功能受损。在 RPL3L 缺陷型心脏中发现 mRNA 密码子的核糖体占有率发生改变，并且这些变化与在过表达 RPL3L 的成肌细胞中观察到的变化呈负相关。与含有 RPL3 的经典核糖体相比，含有 RPL3L 的核糖体不易发生碰撞。尽管缺失含有 RPL3L 的核糖体改变了整个转录组的翻译延伸动力学，但对与心肌收缩和扩张型心肌病相关的转录本的影响最为明显，编码蛋白的丰度相应降低。我们的结果为组织特异性翻译调控的机制和生理相关性提供了进一步的见解。
