Two for the price of one: a bifunctional intron-encoded DNA endonuclease-RNA maturase

Homing endonucleases are enzymes that are typically encoded by intervening sequences of various kinds—introns that splice at the RNA level, or inteins that splice at the protein level (for review, see Belfort et al. 2002). The endonucleases function primarily to mobilize these elements, which are often self-splicing, by facilitating their integration to new sites in DNA. Because these sites are most often allelic intronless or inteinless sites, this form of mobility is termed homing, and the target sequences are termed homing sites.

Homing endonucleases sometimes do double duty, also functioning as maturases, which promote RNA splicing (for review, see Lambowitz and Perlman 1990; Lambowitz and Belfort 1993). Maturases are usually intron specific, and act as cofactors that bind their introncontaining precursor RNA to facilitate splicing. Nevertheless, catalysis required for splicing remains a property of the RNA.

The endonuclease-gene invasion hypothesis

How might a single protein have evolved to process two substrates, DNA and RNA? It is widely held that DNAs encoding self-splicing introns, particularly group I introns, and self-splicing inteins were colonized by endonuclease genes, which are considered the primordial invasive genetic elements (Fig. 1; for review, see Lambowitz and Perlman 1990; Lambowitz and Belfort 1993). Maturase activity is postulated to have been acquired secondarily, as an adaptation by which to minimize the adverse consequences of endonuclease gene invasion on the splicing function of the intron (Fig. 2). This sequence of events would result in a mutualistic relationship, in which the endonuclease gene is afforded a phenotypically neutral hiding place in a self-splicing element, which in turn acquires the ability to spread to new sites via its newly found endonuclease partner that cleaves DNA.