YB-1 autoregulates translation of its own mRNA at or prior to the step of 40S ribosomal subunit joining.
YB-1 is a member of the numerous families of proteins with an evolutionary ancient cold-shock domain. It is involved in many DNA- and RNA-dependent events and regulates gene expression at different levels. Previously, we found a regulatory element within the 3' untranslated region (UTR) of YB-1 mRNA that specifically interacted with YB-1 and poly(A)-binding protein (PABP); we also showed that PABP positively affected YB-1 mRNA translation in a poly(A) tail-independent manner (O. V. Skabkina, M. A. Skabkin, N. V. Popova, D. N. Lyabin, L. O. Penalva, and L. P. Ovchinnikov, J. Biol. Chem. 278:18191-18198, 2003). Here, YB-1 is shown to strongly and specifically inhibit its own synthesis at the stage of initiation, with accumulation of its mRNA in the form of free mRNPs. YB-1 and PABP binding sites have been mapped on the YB-1 mRNA regulatory element. These were UCCAG/ACAA for YB-1 and a approximately 50-nucleotide A-rich sequence for PABP that overlapped each other. PABP competes with YB-1 for binding to the YB-1 mRNA regulatory element and restores translational activity of YB-1 mRNA that has been inhibited by YB-1. Thus, YB-1 negatively regulates its own synthesis, presumably by specific interaction with the 3'UTR regulatory element, whereas PABP restores translational activity of YB-1 mRNA by displacing YB-1 from this element.
Skabkina
Olga V
OV
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia.
Lyabin
Dmitry N
DN
Skabkin
Maxim A
MA
Ovchinnikov
Lev P
LP
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D010442:Peptide Chain Initiation, Translational / Q000235:genetics* / Q000502:physiology; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics* / Q000502:physiology; D012156:Reticulocytes / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051840:Y-Box-Binding Protein 1
D020413:3' Untranslated Regions; D022762:CCAAT-Enhancer-Binding Proteins; D051839:NFI Transcription Factors; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1