Y-box-binding protein 1

Definition:

DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing, DNA repair and transcription regulation. Predominantly acts as a RNA-binding protein: binds preferentially to the 5'-[CU]CUGCG-3' RNA motif and specifically recognizes mRNA transcripts modified by C5-methylcytosine (m5C). Promotes mRNA stabilization: acts by binding to m5C-containing mRNAs and recruiting the mRNA stability maintainer ELAVL1, thereby preventing mRNA decay. Component of the CRD-mediated complex that promotes MYC mRNA stability. Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Plays a key role in RNA composition of extracellular exosomes by defining the sorting of small non-coding RNAs, such as tRNAs, Y RNAs, Vault RNAs and miRNAs. Probably sorts RNAs in exosomes by recognizing and binding C5-methylcytosine (m5C)-containing RNAs. Acts as a key effector of epidermal progenitors by preventing epidermal progenitor senescence: acts by regulating the translation of a senescence-associated subset of cytokine mRNAs, possibly by binding to m5C-containing mRNAs. Also involved in pre-mRNA alternative splicing regulation: binds to splice sites in pre-mRNA and regulates splice site selection. Also able to bind DNA: regulates transcription of 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, suggesting a role in DNA repair. The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation.

References:

[1]. Isabelle Gaudreault, et al. YB-1 promotes strand separation in vitro of duplex DNA containing either mispaired bases or cisplatin modifications, exhibits endonucleolytic activities and binds several DNA repair proteins. Nucleic Acids Res. 2004 Jan 12;32(1):316-27. [Content Brief]

[2]. Doreen Weidensdorfer, et al. Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs. RNA. 2009 Jan;15(1):104-15. [Content Brief]

[3]. Xin Chen, et al. 5-methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs. Nat Cell Biol. 2019 Aug;21(8):978-990. [Content Brief]

[4]. Eunjeong Kwon, et al. The RNA-binding protein YBX1 regulates epidermal progenitors at a posttranscriptional level. Nat Commun. 2018 Apr 30;9(1):1734. [Content Brief]

[5]. Debashish Ray, et al. Rapid and systematic analysis of the RNA recognition specificities of RNA-binding proteins. Nat Biotechnol. 2009 Jul;27(7):667-70. [Content Brief]

[6]. Matthew J Shurtleff, et al. Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. Elife. 2016 Aug 25;5:e19276. [Content Brief]

[7]. Björn C Frye, et al. Y-box protein-1 is actively secreted through a non-classical pathway and acts as an extracellular mitogen. EMBO Rep. 2009 Jul;10(7):783-9. [Content Brief]

[8]. C Y Chen, et al. Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation. Genes Dev. 2000 May 15;14(10):1236-48. [Content Brief]

[9]. Matthew J Shurtleff, et al. Broad role for YBX1 in defining the small noncoding RNA composition of exosomes. Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):E8987-E8995. [Content Brief]

[10]. E E Capowski, et al. Y box-binding factor promotes eosinophil survival by stabilizing granulocyte-macrophage colony-stimulating factor mRNA. J Immunol. 2001 Nov 15;167(10):5970-6. [Content Brief]

[11]. E M Horwitz, et al. A human protein containing a "cold shock" domain binds specifically to H-DNA upstream from the human gamma-globin genes. J Biol Chem. 1994 May 13;269(19):14130-9. [Content Brief]

[12]. Ranajoy Chattopadhyay, et al. Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1. Mol Cell Biol. 2008 Dec;28(23):7066-80. [Content Brief]

[13]. Ute Raffetseder, et al. Splicing factor SRp30c interaction with Y-box protein-1 confers nuclear YB-1 shuttling and alternative splice site selection. J Biol Chem. 2003 May 16;278(20):18241-8. [Content Brief]

[14]. Olga A Kossinova, et al. Cytosolic YB-1 and NSUN2 are the only proteins recognizing specific motifs present in mRNAs enriched in exosomes. Biochim Biophys Acta Proteins Proteom. 2017 Jun;1865(6):664-673. [Content Brief]

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