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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alu Elements / genetics*
  • Animals
  • Base Sequence
  • Biological Evolution
  • Exons / genetics*
  • Humans
  • Introns / genetics
  • Molecular Sequence Data
  • Nuclear Proteins / genetics*
  • Primates / genetics*
  • RNA Editing*
  • Sequence Alignment

Substances

  • NARF protein, human
  • Nuclear Proteins