(A) ETn effects on gene transcript processing. The most common patterns of aberrant transcript processing caused by ETns in gene introns are shown. The natural LTR polyadenylation (polyA) site and a second cryptic polyadenylation site in the internal region, along with four cryptic splice acceptors (SA) and a donor site (SD), are involved in most cases. The number of such cases is an underestimate, since several reports lack sufficient detail of aberrant transcripts. In some cases, several aberrant forms have been found. Boxes denote gene exons, thin lines denote introns, and thick lines denote spliced mRNAs, with direction of transcription from left to right. For clarity, cryptic splice acceptor sites in the 3' LTR are not shown since no documented splicing events involving these sites were found. Intronic mutagenic ETns and the affected gene are most often found in the same orientation (15 of 16 cases).
(B) IAP promoter effects on gene transcription. Ectopic gene expression driven by an antisense promoter in the 5' LTR of an IAP has been reported in eight cases. In some cases, the IAP is located a significant distance upstream of the gene.

IAP and ETn insertions were classified by their mechanism of gene disruption. Well documented instances of aberrant transcription initiation (5'-terminus) and polyadenylation (3'-terminus) were counted, as well as aberrant splicing and exon skipping (internal disruption). Insertions that cause gene disruption by multiple mechanisms (Table S1) were counted once in each relevant class.

Blocks to various stages of the retroviral or LTR retroelement life cycle are depicted as are silencing mechanisms affecting activity of integrated elements. Examples of restriction genes and silencing mechanisms: receptor block, Fv4; uncoating block, Trim5; reverse transcription/trafficking block, APOBEC3 and Fv1; transcription block, CpG methylation; and RNA processing block, Nxf1 and RNAi. See text and Table 2 for more details and other examples. An ERV or LTR element within an intron is shown to illustrate common gene-disruptive effects of such sequences through introduction of polyadenylation sites, promoters, and splice donor and acceptor sites. Spliced RNA is depicted with dashed lines. A normal gene transcript driven by the native promoter (P) is shown below the gene. A full-length retroviral transcript, which could be packaged for further rounds of retrotransposition or retroviral infection, is shown above the gene locus. Various potential aberrant or chimeric transcripts are shown above.