Retrotransposons mobilize via RNA intermediates and usually carry with them the agent of their mobility, reverse transcriptase. Retrotransposons are streamlined, and therefore rely on host factors to proliferate. However, retrotransposons are exposed to cellular forces that block their paths. For this review, we have selected for our focus elements from among target-primed (TP) retrotransposons, also called non-LTR retrotransposons, and extrachromosomally-primed (EP) retrotransposons, also called LTR retrotransposons. The TP retrotransposons considered here are group II introns, LINEs and SINEs, whereas the EP elments considered are the Ty and Tf retrotransposons, with a brief comparison to retroviruses. Recurring themes for these elements, in hosts ranging from microbes to man, are tie-ins of the retrotransposons to RNA metabolism, DNA replication and repair, and cellular stress. Likewise, there are parallels among host-cell defenses to combat rampant retrotransposon spread. The interactions between the retrotransposon and the host, and their co-evolution to balance the tension between retrotransposon proliferation and host survival, form the basis of this review.

SummaryCatalytic group II introns are mobile retroelements that invade cognate intronless genes via retrohoming, where the introns reverse splice into double-stranded DNA (dsDNA) targets. They can also retrotranspose to ectopic sites at low frequencies. Whereas our previous studies with a bacterial intron, Ll.LtrB, supported frequent use of RNA targets during retrotransposition, recent experiments with a retrotransposition indicator gene indicate that DNA, rather than RNA, is a prominent target, with both dsDNA and single-stranded DNA (ssDNA) as possibilities. Thus retrotransposition occurs in both transcriptional sense and antisense orientations of target genes, and is largely independent of homologous DNA recombination and of the endonuclease function of the intronencoded protein, LtrA. Models based on both dsDNA and ssDNA targeting are presented. Interestingly, retrotransposition is biased toward the template for lagging-strand DNA synthesis, which suggests the possibility of the replication folk as a source of ssDNA. Consistent with some use of ssDNA targets, many retrotransposition sites lack nucleotides critical for the unwinding of target duplex DNA. Moreover, in vitro the intron reverse spliced into ssDNA more efficiently than dsDNA substrates for some of the retrotransposition sites. Furthermore, many bacterial group II introns reside on the lagging-strand template, hinting at a role for DNA replication in intron dispersal in nature.

SummaryGroup II introns are mobile retroelements that invade their cognate intron-minus gene in a process known as retrohoming. They can also retrotranspose to ectopic sites at low frequency. Previous studies of the Lactococcus lactis intron Ll.LtrB indicated that in its native host, as in Escherichia coli , retrohoming occurs by the intron RNA reverse splicing into double-stranded DNA (dsDNA) through an endonucleasedependent pathway. However, in retrotransposition in L. lactis , the intron inserts predominantly into single-stranded DNA (ssDNA), in an endonucleaseindependent manner. This work describes the retrotransposition of the Ll.LtrB intron in E. coli , using a retrotransposition indicator gene previously employed in our L. lactis studies. Unlike in L. lactis , in E. coli , Ll.LtrB retrotransposed frequently into dsDNA, and the process was dependent on the endonuclease activity of the intron-encoded protein.Further, the endonuclease-dependent insertions preferentially occurred around the origin and terminus of chromosomal DNA replication. Insertions in E. coli can also occur through an endonucleaseindependent pathway, and, as in L. lactis , such events have a more random integration pattern. Together these findings show that Ll.LtrB can retrotranspose through at least two distinct mechanisms and that the host environment influences the choice of integration pathway. Additionally, growth conditions affect the insertion pattern. We propose a model in which DNA replication, compactness of the nucleoid and chromosomal localization influence target site preference.