Dataset Information

YBX3 is a versatile RNA-binding protein that controls amino acid import by regulating SLC mRNA abundance

ABSTRACT: Summary: Amino acids (AA) support protein synthesis, and thus cell growth and proliferation. Specialized transporters mediate AA exchange across membranes and their regulation is critical for AA homeostasis. Here, we report that the DNA- and RNA-binding protein YBX3 regulates the expression of AA transporters. To investigate the functions of YBX3, we integrated proteomics and transcriptomics data with YBX3-RNA complex data to identify RNAs directly regulated by YBX3. The data revealed YBX3 as a versatile RNA-binding protein (RBP) that regulates as both a translational repressor and mRNA stabilizer. Among the direct YBX3 targets, we We identified two solute carrier (SLC) AA transporters (SLC7A5 and SLC3A2). We show that YBX3 stabilizes these SLC mRNAs and that the 3 UTR of SLC7A5 is necessary and sufficient for YBX3-mediated regulation. Further, YBX3 depletion results in diminished intracellular levels of SLC7A5/SLC3A2 substrates, large neutral AA. Importantly, expression of an exogenous SLC7A5 not susceptible to YBX3 regulation restores AA levels. Thus, YBX3 is a key post-transcriptional regulator of large neutral AA import.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Gertjan Kramer

PROVIDER: MSV000083108 | MassIVE | Tue Nov 06 08:30:00 GMT 2018

SECONDARY ACCESSION(S): PXD011592

REPOSITORIES: MassIVE

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

Cooke Amy A Schwarzl Thomas T Huppertz Ina I Kramer Gertjan G Mantas Panagiotis P Alleaume Anne-Marie AM Huber Wolfgang W Krijgsveld Jeroen J Hentze Matthias W MW

Cell reports 20190601 11

Sufficient amino acid supplies are critical for protein synthesis and, thus, cell growth and proliferation. Specialized transporters mediate amino acid exchange across membranes and their regulation is critical for amino acid homeostasis. Here, we report that the DNA- and RNA-binding protein YBX3 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 s ...[more]

PMID: 31189097

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