#DOTD: Long Terminal Repeat

9 Sep 2017

Long Terminal Repeats (LTRs) are features of LTR retrotransposons + double-stranded proviral DNA (result of reverse transcription of single-stranded retroviral RNA).

 

Importantly, LTRs are direct repeats which flank the transposed coding regions + themselves are flanked by Target Site Duplications (TSDs).

 

Their structure comprises three domains: U3, R + U5. U3 and U5 contain signals for synthesis + processing of the retroviral genome/retrotransposon; R, usually 10 to 230bp in length, "is necessary for DNA strand transfer during reverse transcription". [6]

 

It should be noted that extremely high sequence conservation has been observed in the two bases at each of the 3' + 5' termini of all human LTRs. [7]

 

In wheat retrotransposon Wis 2-1A, the length of the LTR is unusually long: 1755bp [3]. Interestingly, approximately 45% of these LTR structures are comprised of hairpins, caused by inverted repeats (gapped palindromes).

 

Why do we care about LTRs? Here is one incredible reason: LTR-targeted mutation of the HIV-1 provirus using CRISPR/Cas9 has been shown [4] to reduce LTR-driven expression of the virus!

 

[249]

 

References:

1. https://en.wikipedia.org/wiki/Long_terminal_repeat

2. http://gydb.org/index.php/LTRs_and_TIRs [great article explaining the difference between LTRs and Terminal Inverted Repeats (TIRs)]

3. Lucas, H., Moore, G., Murphy, G. and Flavell, R.B., 1992. Inverted repeats in the long-terminal repeats of the wheat retrotransposon Wis 2-1A. Molecular biology and evolution, 9(4), pp.716-728.

4. Ebina, H., Misawa, N., Kanemura, Y. and Koyanagi, Y., 2013. Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus. Scientific reports, 3.

5. Shah, S., Alexaki, A., Pirrone, V., Dahiya, S., Nonnemacher, M.R. and Wigdahl, B., 2014. Functional properties of the HIV-1 long terminal repeat containing single-nucleotide polymorphisms in Sp site III and CCAAT/enhancer binding protein site I. Virology journal, 11(1), p.92.

6. Howe, M. and Berg, D., 1989. Mobile DNA. Amer Soc Microbiol, Washington DC. [see chapter 3]

7. Lee, I. and Harshey, R.M., 2003. Patterns of sequence conservation at termini of long terminal repeat (LTR) retrotransposons and DNA transposons in the human genome: lessons from phage Mu. Nucleic acids research, 31(15), pp.4531-4540.

8. Jeeninga, R.E., Hoogenkamp, M., Armand-Ugon, M., de Baar, M., Verhoef, K. and Berkhout, B.E.N., 2000. Functional differences between the long terminal repeat transcriptional promoters of human immunodeficiency virus type 1 subtypes A through G. Journal of virology, 74(8), pp.3740-3751.

 

 

 

 

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