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      Beyond DNA: RNA editing and steps toward Alu exonization in primates.

      Journal of Molecular Biology
      Alu Elements, genetics, Animals, Base Sequence, Biological Evolution, Exons, Humans, Introns, Molecular Sequence Data, Nuclear Proteins, Primates, RNA Editing, Sequence Alignment

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          Abstract

          The exaptation of transposed elements into protein-coding domains by a process called exonization is one important evolutionary pathway for generating novel variant functions of gene products. Adenosine-to-inosine (A-to-I) modification is a recently discovered, RNA-editing-mediated mechanism that contributes to the exonization of previously unprocessed mRNA introns. In the human nuclear prelamin A recognition factor gene transcript, the alternatively spliced exon 8 results from an A-to-I editing-generated 3' splice site located within an intronic Alu short interspersed element. Sequence comparisons of representatives of all primate infraorders revealed the critical evolutionary steps leading to this editing-mediated exonization. The source of exon 8 was seeded within the primary transcript about 58-40 million years ago by the head-to-head insertions of two primate-specific Alu short interspersed elements in the common ancestor of anthropoids. The latent protein-coding potential was realized 34-52 million years later in a common ancestor of gorilla, chimpanzee, and human as a result of numerous changes at the RNA and DNA level. Comparisons of 426 processed mRNA clones from various primate species with their genomic sequences identified seven different RNA-editing-mediated alternative splice variants. In total, 30 A-to-I editing sites were identified. The gorilla, chimpanzee, and human nuclear prelamin A recognition factor genes exemplify the versatile interplay of pre- and posttranscriptional modifications leading to novel genetic potential.

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          Author and article information

          Journal
          18680752
          10.1016/j.jmb.2008.07.014

          Chemistry
          Alu Elements,genetics,Animals,Base Sequence,Biological Evolution,Exons,Humans,Introns,Molecular Sequence Data,Nuclear Proteins,Primates,RNA Editing,Sequence Alignment

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