The RNA-Binding Protein YBX3 Controls Amino Acid Levels by Regulating SLC mRNA Abundance

Summary Sufficient amino acidsupplies are critical for protein synthesis and, thus, cell growth and proliferation. Specialized transporters mediate amino acidexchange across membranes and their regulation is critical for amino acidhomeostasis. Here, we report that the DNA- and RNA-binding proteinYBX3 regulates the expression of amino acid transporters. To investigate the functions of YBX3, we integrated proteomic and transcriptomic data from cells depleted of YBX3 with analyses of YBX3 RNA binding sites to identify RNAs directly regulated by YBX3. The data implicate YBX3 as a RNA-binding proteinthat regulates distinct sets of mRNAs by discrete mechanisms, including mRNA abundance. Among direct YBX3 targets, two solute carrier (SLC) amino acid transporters(SLC7A5 and SLC3A2) were identified. We show that YBX3 stabilizes these SLC mRNAs and that YBX3 depletion diminishes the expression of SLC7A5/SLC3A2, which specifically reduces SLC7A5/SLC3A2 amino acidsubstrates. Thus, YBX3 emerges as a key regulator of amino acidlevels.