Long terminal repeat
A long terminal repeat (LTR) is a pair of identical sequences of DNA, several hundred base pairs long, which occur in eukaryotic genomes on either end of a series of genes or pseudogenes that form a retrotransposon or an endogenous retrovirus or a retroviral provirus. All retroviral genomes are flanked by LTRs, while there are some retrotransposons without LTRs. Typically, an element flanked by a pair of LTRs will encode a reverse transcriptase and an integrase, allowing the element to be copied and inserted at a different location of the genome. Copies of such an LTR-flanked element can often be found hundreds or thousands of times in a genome. LTR retrotransposons comprise about 8% of the human genome.[1]
The first LTR sequences were found by A.P. Czernilofsky and J. Shine in 1977 and 1980.[2][3]
Transcription
The LTR-flanked sequences are partially
Retroviruses such as human immunodeficiency virus (HIV) use this basic mechanism.
Dating retroviral insertions
As 5' and 3' LTRs are identical upon insertion, the difference between paired LTRs can be used to estimate the age of ancient retroviral insertions. This method of dating is used by paleovirologists, though it fails to take into account confounding factors such as gene conversion and homologous recombination.[4]
HIV-1
The
All of the required signals for gene expression are found in the LTRs: Enhancer, promoter (can have both transcriptional enhancers or regulatory elements), transcription initiation (such as capping), transcription terminator and polyadenylation signal.[7]
In HIV-1, the
- TAR, or trans-activation response element, plays a critical role in transcriptional activation via its interaction with viral proteins. It forms a highly stable stem–loop structure consisting of 26 base pairs with a bulge in its secondary structure that interfaces with the viral transcription activator protein Tat.[8]
- Poly A plays roles both in dimerization and genome packaging since it is necessary for cleavage and polyadenylation. It has been reported that sequences upstream (U3 region) and downstream (U5 region) are needed in order to make the cleavage process efficient.[9]
- PBS, or primer binding site, is 18 nucleotides long and has a specific sequence that binds to the tRNALys primer required for initiation of reverse transcription.[10]
- Psi (Ψ), or the
- DIS, or dimer initiation site, is a highly conserved RNA–RNA interacting sequence constituting the SL1 stem–loop in the Psi packaging element of many retroviruses. DIS is characterized by a conserved stem and palindromic loop that forms a kissing-loop complex between HIV-1 RNA genomes to dimerize them for encapsidation.[12]
The transcript begins, at the beginning of R, is capped, and proceeds through U5 and the rest of the provirus, usually terminating by the addition of a poly A tract just after the R sequence in the 3' LTR.
The finding that both HIV LTRs can function as transcriptional promoters is not surprising since both elements are apparently identical in nucleotide sequence. Instead, the 3' LTR acts in transcription termination and polyadenylation. However, it has been suggested that the transcriptional activity of the 5' LTR is far greater than that of the 3' LTR, a situation that is very similar to that of other retroviruses.[7]
During transcription of the human immunodeficiency virus type 1 provirus, polyadenylation signals present in the 5' long terminal repeat (LTR) are disregarded while the identical polyadenylation signals present in the 3'LTR are utilized efficiently. It has been suggested that transcribed sequences present within the HIV-1 LTR U3 region act in cis to enhance polyadenylation within the 3' LTR.[13]
See also
References
- .
- PMID 67601.
- PMID 6253899.
- PMID 28672160.
- ^ Human Retroviruses and AIDS, 1998.
- ^ Krebs, Fred C.; Hogan, Tricia H.; Quiterio, Shane; Gartner, Suzanne; Wigdahl, Brian (2001). "Lentiviral LTR-directed Expression, Sequence Variation, and Disease Pathogenesis" (PDF). In Kuiken, C; Foley, B; B; Marx, P; McCutchan, F; Mellors, JW; Wolinsky, S; Korber, B (eds.). HIV Sequence Compendium 2001. Los Alamos, NM: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory. pp. 29–70.
- ^ PMID 8189520.
- PMID 15219234.
- PMID 1508176.
- PMID 12194974.
- PMID 20949075.
- PMID 22306406.
- PMID 1851882.
External links
- Media related to Long terminal repeat at Wikimedia Commons
- Long+Terminal+Repeat at the U.S. National Library of Medicine Medical Subject Headings (MeSH)