Beyond DNA: RNA Editing and Steps Toward Alu Exonization in Primates

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 co...

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Bibliographic Details
Published in:Journal of molecular biology 2008-10, Vol.382 (3), p.601-609
Main Authors: Möller-Krull, Maren, Zemann, Anja, Roos, Christian, Brosius, Jürgen, Schmitz, Jürgen
Format: Article
Language:English
Subjects:
A-to-I RNA-editing
alternative splicing
Alu Elements - genetics
Alu exonization
Animals
Base Sequence
Biological Evolution
Exons - genetics
Humans
Introns - genetics
Molecular Sequence Data
nuclear prelamin A recognition factor (NARF)
Nuclear Proteins - genetics
Pan troglodytes
Primates
Primates - genetics
RNA Editing
Sequence Alignment
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Summary: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.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2008.07.014