6ktc
From Proteopedia
Crystal structure of YBX1 CSD with m5C RNA
Structural highlights
FunctionYBOX1_HUMAN Mediates pre-mRNA alternative splicing regulation. Binds to splice sites in pre-mRNA and regulates splice site selection. Binds and stabilizes cytoplasmic mRNA. Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Regulates the transcription of numerous genes. Its transcriptional activity on the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7'. Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes. Promotes separation of DNA strands that contain mismatches or are modified by cisplatin. Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA (in vitro). May play a role in DNA repair. Component of the CRD-mediated complex that promotes MYC mRNA stability. Binds preferentially to the 5'-[CU]CUGCG-3' motif in vitro.[1] [2] [3] [4] [5] [6] [7] [8] The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation. Publication Abstract from PubMed5-Methylcytosine (m(5)C) is a RNA modification that exists in tRNAs and rRNAs and was recently found in mRNAs. Although it has been suggested to regulate diverse biological functions, whether m(5)C RNA modification influences adult stem cell development remains undetermined. In this study, we show that Ypsilon schachtel (YPS), a homolog of human Y box binding protein 1 (YBX1), promotes germ line stem cell (GSC) maintenance, proliferation, and differentiation in the Drosophila ovary by preferentially binding to m(5)C-containing RNAs. YPS is genetically demonstrated to function intrinsically for GSC maintenance, proliferation, and progeny differentiation in the Drosophila ovary, and human YBX1 can functionally replace YPS to support normal GSC development. Highly conserved cold-shock domains (CSDs) of YPS and YBX1 preferentially bind to m(5)C RNA in vitro. Moreover, YPS also preferentially binds to m(5)C-containing RNAs, including mRNAs, in germ cells. The crystal structure of the YBX1 CSD-RNA complex reveals that both hydrophobic stacking and hydrogen bonds are critical for m(5)C binding. Overexpression of RNA-binding-defective YPS and YBX1 proteins disrupts GSC development. Taken together, our findings show that m(5)C RNA modification plays an important role in adult stem cell development. Drosophila YBX1 homolog YPS promotes ovarian germ line stem cell development by preferentially recognizing 5-methylcytosine RNAs.,Zou F, Tu R, Duan B, Yang Z, Ping Z, Song X, Chen S, Price A, Li H, Scott A, Perera A, Li S, Xie T Proc Natl Acad Sci U S A. 2020 Feb 3. pii: 1910862117. doi:, 10.1073/pnas.1910862117. PMID:32015133[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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