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LTR Retrotransposons
LTR retrotransposons are class I transposable elements with long terminal repeats flanking an internal coding region. These elements are less abundant…
Most eukaryotic genomes contain a unique group of transposable elements called Retrotransposons, or Class I transposons.
Unlike DNA-only transposons or Class II transposons, the retrotransposons employ a "copy and paste" mechanism - which means that a copy of the transposon moves to a new site on the genome.
There are two types of retrotransposons - Long terminal repeat, or LTR, retrotransposons, and non-LTR retrotransposons - both of which use different transposition mechanisms.
The LTR retrotransposons consist of a 5-7kb long protein-coding region flanked at both ends by long terminal repeats, typically 250-600 bp in length.
These LTRs contain enhancer and promoter sequences for transcription.
The coding region is very similar to that of the retroviral genome, consisting of genes closely related to the gag and pol of retroviruses. Hence, LTR retrotransposons are also known as retroviral-like retrotransposons.
However, unlike retroviruses, LTR retrotransposons do not encode the “env” gene, and hence, cannot form a viral envelope.
While the pol gene encodes enzymes such as protease, reverse transcriptase, integrase, and RNase H; the gag gene encodes structural proteins that can form a virus-like particle.
The mechanism of transposition of the LTR elements also resembles retroviral replication in the host cells.
First, the host cell RNA Polymerase II binds to the 5’ LTR and starts transcribing the retrotransposon into a single RNA strand.
The RNA intermediate is then processed by the host cell enzymes to add a 5’ cap and a 3’ polyA tail.
The mature RNA is then transported to the cytoplasm and translated into proteins. The mRNA and the protein products then assemble to form a virus-like particle. It is inside this virus-like particle that the RNA is reverse transcribed into a single-stranded DNA copy.
This is followed by the degradation of the RNA strand by RNase H, and synthesis of a complementary DNA strand leading to a double-stranded DNA.
This linear, double-stranded DNA is bound by the integrase at both ends to form a stable complex called an intasome that can be transported back into the nucleus and inserted into a new location on the host genome.
LTR retrotransposons can make several copies of themselves in the same cell using this mechanism of replication.
Q1: What is the structure of an LTR retrotransposon?
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.
Q2: How do LTR retrotransposons differ from DNA-only transposons?
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.
Q3: What proteins do LTR retrotransposons encode?
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.
Q4: What is the role of the virus-like particle in LTR retrotransposon transposition?
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.
Q5: How does integrase function in LTR retrotransposon insertion?
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.
Q6: Why can't LTR retrotransposons form infectious virions like retroviruses?
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.
Q7: What percentage of human DNA consists of LTR retrotransposons?
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.