title: A trinucleotide repeat-associated increase in the level of Alu RNA-binding protein occurred during the same period as the major Alu amplification that accompanied anthropoid evolution.
abstract: Nearly 1 million Alu elements in human DNA were inserted by an RNA-mediated retroposition-amplification process that clearly decelerated about 30 million years ago. Since then, Alu sequences have proliferated at a lower rate, including within the human genome, in which Alu mobility continues to generate genetic variability. Initially derived from 7SL RNA of the signal recognition particle (SRP), Alu became a dominant retroposon while retaining secondary structures found in 7SL RNA. We previously identified a human Alu RNA-binding protein as a homolog of the 14-kDa Alu-specific protein of SRP and have shown that its expression is associated with accumulation of 3'-processed Alu RNA. Here, we show that in early anthropoids, the gene encoding SRP14 Alu RNA-binding protein was duplicated and that SRP14-homologous sequences currently reside on different human chromosomes. In anthropoids, the active SRP14 gene acquired a GCA trinucleotide repeat in its 3'-coding region that produces SRP14 polypeptides with extended C-terminal tails. A C-->G substitution in this region converted the mouse sequence CCA GCA to GCA GCA in prosimians, which presumably predisposed this locus to GCA expansion in anthropoids and provides a model for other triplet expansions. Moreover, the presence of the trinucleotide repeat in SRP14 DNA and the corresponding C-terminal tail in SRP14 are associated with a significant increase in SRP14 polypeptide and Alu RNA-binding activity. These genetic events occurred during the period in which an acceleration in Alu retroposition was followed by a sharp deceleration, suggesting that Alu repeats coevolved with C-terminal variants of SRP14 in higher primates.
authors.affiliation: Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2753.
authors.forename: D Y
authors.initials: DY
authors.lastname: Chang
authors.forename: N
authors.initials: N
authors.lastname: Sasaki-Tozawa
authors.forename: L K
authors.initials: LK
authors.lastname: Green
authors.forename: R J
authors.initials: RJ
authors.lastname: Maraia
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002877:Chromosomes, Human / Q000235:genetics; D006071:Gorilla gorilla; D000882:Haplorhini / Q000235:genetics*; D006801:Humans; D051379:Mice; D005810:Multigene Family; D002679:Pan troglodytes; D010215:Papio; D011148:Pongo pygmaeus; D012313:RNA / Q000235:genetics*; D020733:RNA, Small Cytoplasmic; D016601:RNA-Binding Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D018271:Signal Recognition Particle / Q000235:genetics*
chemical_list: D020733:RNA, Small Cytoplasmic; D016601:RNA-Binding Proteins; C490326:SRP14 protein, human; D018271:Signal Recognition Particle; C490325:Srp14 protein, mouse; C503637:Srp72 protein, mouse; D012313:RNA