The YBX3 RNA-binding protein posttranscriptionally controls SLC1A5 mRNA in proliferating and differentiating skeletal muscle cells.
The YBX3 RNA-binding protein posttranscriptionally controls SLC1A5 mRNA in proliferating and differentiating skeletal muscle cells.
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DOI：
10.1016/j.jbc.2023.105602
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发表时间：
2024-02
影响因子：
4.8
通讯作者：
Cooke, Amy
中科院分区：
文献类型：
--
作者：
Awad, Silina;Skipper, William;Vostrejs, William;Ozorowski, Kendall;Min, Kristen;Pfuhler, Liva;Mehta, Darshan;Cooke, Amy
在人类中，骨骼肌占总体重的近40%，整个成年期通过肌肉蛋白质合成和分解的平衡来维持这一比例。细胞氨基酸(AA)水平对这些过程至关重要，哺乳动物细胞含有转运蛋白，这些转运蛋白输入氨基酸以维持体内平衡。直到最近，转运蛋白调控的控制主要是在转录和翻译后水平上进行的研究。然而，在这里，我们报告了RNA结合蛋白YBX3对于维持小鼠骨骼肌细胞内AAs的关键，这与我们最近在人类细胞中的发现一致。我们发现YBX3直接与溶质载体(SLC)1A5 AA转运体信使(M)RNA结合，在骨骼肌细胞分化过程中转录后调控SLC1A5的表达。YBX3对SLC1A5的调控需要3‘非编码区。此外，当YBX3耗尽时，SLC1A5直接或间接通过连接到其他转运体运输的细胞内氨基酸被特别减少。此外，我们发现YBX3蛋白的减少减少了骨骼肌细胞的增殖并损害了分化，并且YBX3和SLC1A5蛋白在骨骼肌分化过程中的表达显著增加，与它们各自的mRNA水平无关。综上所述，我们的研究结果表明，YBX3调节骨骼肌细胞中AA的运输，其表达对于维持骨骼肌细胞的增殖和分化至关重要。
In humans, skeletal muscles comprise nearly 40% of total body mass, which is maintained throughout adulthood by a balance of muscle protein synthesis and breakdown. Cellular amino acid (AA) levels are critical for these processes, and mammalian cells contain transporter proteins that import AAs to maintain homeostasis. Until recently, the control of transporter regulation has largely been studied at the transcriptional and posttranslational levels. However, here, we report that the RNA-binding protein YBX3 is critical to sustain intracellular AAs in mouse skeletal muscle cells, which aligns with our recent findings in human cells. We find that YBX3 directly binds the solute carrier (SLC)1A5 AA transporter messenger (m)RNA to posttranscriptionally control SLC1A5 expression during skeletal muscle cell differentiation. YBX3 regulation of SLC1A5 requires the 3′ UTR. Additionally, intracellular AAs transported by SLC1A5, either directly or indirectly through coupling to other transporters, are specifically reduced when YBX3 is depleted. Further, we find that reduction of the YBX3 protein reduces proliferation and impairs differentiation in skeletal muscle cells, and that YBX3 and SLC1A5 protein expression increase substantially during skeletal muscle differentiation, independently of their respective mRNA levels. Taken together, our findings suggest that YBX3 regulates AA transport in skeletal muscle cells, and that its expression is critical to maintain skeletal muscle cell proliferation and differentiation.
影响因子：
4.6
作者：
Zhao Y;Albrecht E;Stange K;Li Z;Schregel J;Sciascia QL;Metges CC;Maak S
通讯作者：
Maak S