Human Alu sequences are short interspersed DNA elements which have been greatly amplified by retrotransposition. Although initially derived from the 7SL RNA component of signal recognition particle (SRP), the Alu sequence has evolved into a dominant transposon while retaining a specific secondary structure found in 7SL RNA. We previously characterized a set of Alu sequences which are expressed as small cytoplasmic RNAs and isolated a protein that binds to these transcripts. Here we report that biochemical purification of this protein revealed it as the human homolog of the SRP 14 polypeptide which binds the Alu-homologous region of 7SL RNA. The human cDNA predicts an alanine-rich C-terminal tail translated from a trinucleotide repeat not found in the rodent homolog, which accounts for why the human protein-RNA complex migrates more slowly than its rodent counterpart in RNA mobility shift assays. The human Alu RNA-binding protein (RBP) is expressed after transfection of this cDNA into mouse cells. Expression of human RBP in rodent x human somatic cell hybrids is associated with substantial increase in endogenous small cytoplasmic Alu and scBl transcripts but not other small RNAs. These studies provide evidence that this RBP associates with Alu transcripts in vivo and affects their metabolism and suggests a role for Alu transcripts in translation in an SRP-like manner. Analysis of hybrid lines indicated that the Ahu RBP gene maps to human chromosome 15q22, which was confirmed by Southern blotting. The possibility that the primate-specific structure of this protein may have contributed to Alu evolution is considered.Alu sequences are short transposed elements endogenous to the human genome (24, 55). These elements have accumulated to nearly 1 million copies comprising approximately 5% of human DNA. Alu repeats have sequence homology with and are believed to have been derived from the Alu-homologous region of the 7SL RNA component of signal recognition particle (SRP) (64,69,70,71). The current model of Alu evolution suggests that two independently derived Alu-homologous domains of 7SL dimerized to form the more efficient transposing element known as Alu (26,28,45,46,47). Since then, Alu repeats have continued to evolve within primate genomes. A major advance in understanding Alu mobility was the result of work by researchers in several laboratories who classified Alu repeats into subfamilies according to their evolutionary relatedness as determined by sequence homology (8,27,45,59,72). This, together with recent phylogenetic evidence, indicates that multiple Alu source genes continue to spawn new transposed elements (22, 25, 31, 39, 42, 67; reviewed in reference 49).Why genetic elements with disruptive potential have been allowed to proliferate to high copy number in human DNA remains enigmatic. Perhaps Alu mobility improves adaptability of the host genome, or perhaps Alu DNA elements or their RNA products have adopted a function(s) which more directly benefits their host cells (9,19,51,74). Given their short lengt...

Human Alu sequences are short interspersed DNA elements which have been greatly amplified by retrotransposition. Although initially derived from the 7SL RNA component of signal recognition particle (SRP), the Alu sequence has evolved into a dominant transposon while retaining a specific secondary structure found in 7SL RNA. We previously characterized a set of Alu sequences which are expressed as small cytoplasmic RNAs and isolated a protein that binds to these transcripts. Here we report that biochemical purification of this protein revealed it as the human homolog of the SRP 14 polypeptide which binds the Alu-homologous region of 7SL RNA. The human cDNA predicts an alanine-rich C-terminal tail translated from a trinucleotide repeat not found in the rodent homolog, which accounts for why the human protein-RNA complex migrates more slowly than its rodent counterpart in RNA mobility shift assays. The human Alu RNA-binding protein (RBP) is expressed after transfection of this cDNA into mouse cells. Expression of human RBP in rodent x human somatic cell hybrids is associated with substantial increase in endogenous small cytoplasmic Alu and scB1 transcripts but not other small RNAs. These studies provide evidence that this RBP associates with Alu transcripts in vivo and affects their metabolism and suggests a role for Alu transcripts in translation in an SRP-like manner. Analysis of hybrid lines indicated that the Alu RBP gene maps to human chromosome 15q22, which was confirmed by Southern blotting. The possibility that the primate-specific structure of this protein may have contributed to Alu evolution is considered.

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