title: Beyond DNA: RNA editing and steps toward Alu exonization in primates.
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.
authors.affiliation: Institute of Experimental Pathology (ZMBE), University of Münster, Von-Esmarch-Str. 56, 48149 Münster, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Möller-Krull
authors.forename: Anja
authors.initials: A
authors.lastname: Zemann
authors.forename: Christian
authors.initials: C
authors.lastname: Roos
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brosius
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schmitz
mesh_terms: D020087:Alu Elements / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D005091:Exons / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D011323:Primates / Q000235:genetics*; D017393:RNA Editing; D016415:Sequence Alignment
chemical_list: C400022:NARF protein, human; D009687:Nuclear Proteins