Structure of an intronless mouse nucleolin pseudogene: insights into mechanisms enabling the conversion of RNA to DNA

The complete nucleotide (nt) sequence of a mouse nucleolin (Nuc) pseudogene (termed E4) is reported. The E4 element displays the hallmarks of retroposons generated from processed RNA messages, i.e., lack of introns (out of 14 in the active nuc gene), presence of a poly(dA) tail at the 3' end, and is a short directly repeated sequence (TTCTAATATTTGA) at both ends. In addition, the genetic information corresponding to the 5' part of the nuc mRNA is missing. The most salient feature is the presence in the 3' half of the terminal direct repeats of a motif (TTTGA) corresponding precisely to the nuc messenger sequence at the truncation site. This unusual structure suggests that the E4 pseudogene, which appeared in the mouse genome about 15 Myr ago, arose from an insertion event involving a weak hybridization between a recipient DNA and a nuc mRNA-like intermediate. This hypothesis is supported by the fact that the chromosomal integration site is enriched in A and T residues and contains sequences capable of adopting a Z-DNA conformation. On the basis of these data, an RNA-mediated transposition model involving a strand switch during the retrotranscription process is proposed.