The vertebrate Y-box proteins Structure and nucleic acid recognition
The eukaryotic Y-box proteins were initially characterized through their interaction with duplex DNA containing the sequence CAAT('-7). The deduced amino acid sequence for the vertebrate proteins revealed an almost identically conserved 78-amino-acid-long region (>90% identity), that was subsequently defined as conferring the nucleic acid recognition properties of the proteind7). Thus it is probable that all these vertebrate Y-box proteins will show comparable nucleic acid recognition specificities. The stable interaction of the Y-box proteins with radiolabelled duplex DNA was shown using DNase I footprinting and other binding assayd437).
The human protein YBl was found to have relative specificity for duplex DNA containing the sequence CTGATTGG% C/~AA, known as the Y-box (Fig. l)(l). This regulatory sequence, containing a reverse CAAT box (ATTG), is found in the transcriptional control regions of a variety of eukaryotic genes, including those of mammalian major histocompatibility complex class I1 genes and vertebrate gamete-specific genes(*-lo). However, identical or highly related Y-box proteins were subsequently defined through their selective interaction with double-stranded DNA containing pyrimidine (CT)-rich elements(' 1-14), single-stranded DNA(l0,I2), apurinic and mRNA(I7-l9). These diverse interactions with both doubleand single-stranded DNA are summarized in Fig. 1. General conclusions are that: (1) the Y-box proteins prefer to interact with pyrimidine-rich rather than with purine-rich singlestranded DNA; (2) they prefer to bind to duplex DNA in which the two strands of the double helix show a separate enrichment in purine or pyrimidine bases; (3) this preference for purine or pyrimidine enrichment exceeds that for the Ybox element itself; (4) the Y-box sequence is favored for binding over sequences in which it is mutated; (5) some, but not all, single-stranded DNA sequences are favored for binding over duplex DNA.
An important discovery with respect to the function of the vertebrate Y-box proteins was that certain members of the family interact with RNA as part of their in vivo biological role. A Xenopus Y-box protein, FRGY2, was found to have homology to mRNA binding proteins in Xenopus oocytes(6~17,20,21). Earlier work had suggested a selective interaction of these proteins with particular maternal mRNAs( 22). However the Y-box proteins were also believed to bind every 40 nucleotides along the mRNA polynucleotide chain( 23) and hence could have little primary sequence selectivity. Competition experiments demonstrated that FRGY2 will interact with a wide variety of RNA sequences, yet prefers to interact with mixed polymers: poly(C, U), poly(A, C) and poly(A, U), rather than with homopolymers such as p~ly(A)(*~). This selectivity may be important in maintaining the poly(A) tail of eukaryotic mRNA free from interaction with the Y-box proteins (see later).
This diversity of nucleic acid recognition has led to the proposal of diverse functions for the vertebrate Y-box proteins (Table l)(1-7%10-18). However, with the exception of the
Summary
The Y-box proteins are the most evolutionarily conserved nucleic acid binding proteins yet defined in bacteria, plants and animals. The central nucleic acid binding domain of the vertebrate proteins is 43% identical to a 70-amino-acid-long protein (CS7.4) from E. coli. The structure of this domain consists of an antiparallel fivestranded 0-barrel that recognizes both DNA and RNA. The diverse biological roles of these Y-box proteins range from the control of the E. coli cold-shock stress response to the translational masking of messenger RNA in vertebrate gametes. This review discusses the organization of the prokaryotic and eukaryotic Y-box proteins, how they interact with nucleic acids, and their biological roles, both proven and potential. Nucleic Acid Ligands Homo sapiens Mu8 musculus Gallus gallus YB1 /dpbA ATTTTTCTGEGGCCAAAG