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J Mol Biol. 2008 Oct 10;382(3):601-9. doi: 10.1016/j.jmb.2008.07.014. Epub 2008 Jul 16.

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

Author information

1
Institute of Experimental Pathology (ZMBE), University of Münster, Von-Esmarch-Str. 56, 48149 Münster, Germany.

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.

PMID:
18680752
DOI:
10.1016/j.jmb.2008.07.014
[Indexed for MEDLINE]

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