LTR Retrotransposons

LTR retrotransposons consist of a 5-7 kilobase protein-coding region flanked by long terminal repeats (LTRs) of 250-600 base pairs. These LTRs contain enhancer and promoter sequences that regulate transcription. The internal coding region resembles retroviral genomes, encoding gag and pol genes but lacking the env gene found in retroviruses.

LTR retrotransposons use a copy-and-paste mechanism via an RNA intermediate, whereas DNA-only transposons autonomous transposons move directly as DNA. LTR elements are transcribed into RNA, reverse transcribed back into DNA, and inserted into new genomic locations, allowing multiple copies to accumulate within a single cell.

The pol gene encodes enzymes including protease, reverse transcriptase, integrase, and RNase H, which are essential for transposition. The gag gene encodes structural proteins that assemble into virus-like particles. These proteins facilitate the conversion of RNA intermediates into double-stranded DNA and integration into the genome.

The virus-like particle serves as a compartment where reverse transcription occurs. Structural proteins encoded by the gag gene assemble with the RNA intermediate to form this particle. Inside, reverse transcriptase converts the RNA into single-stranded DNA, followed by RNase H degradation of the RNA and synthesis of complementary DNA strands.

Integrase binds to both ends of the linear double-stranded DNA produced by reverse transcription, forming a stable protein-DNA complex called an intasome. This complex is transported back into the nucleus and inserted into a new genomic location, completing the transposition cycle and allowing the element to establish itself at a new site.

LTR retrotransposons lack the env gene required to synthesize a viral envelope, preventing them from forming infectious virions. Without an envelope, these elements cannot exit the cell or move horizontally between cells. They remain confined to transposition within the genome of a single cell, unlike retroviruses and retrotransposons that have acquired envelope genes.

Approximately 8 percent of human genomic DNA comprises LTR retrotransposons. These elements are less abundant in mammals compared to other Class I transposable elements. In humans, the most common LTR retrotransposons are endogenous retroviruses (ERVs), which originated from ancestral viral infections and now play roles in regulatory networks.