LTRs and TIRs
Long Terminal Repeats (LTRs) and Terminal Inverted Repeats (TIRs) are two different kinds of genomic repeats typically related with mobile genetic elements. LTRs are direct repeats that can be found in retroelements (class I of transposable elements) while TIRs are characteristic of DNA-based transposons (classII). LTRs and TIRs play important roles in transposition.
LTRs
The Long Terminal Repeats (LTRs) are two normally homologous non-coding DNA sequences that flank the internal region of certain retrotranscribing mobile genetic elements and that usually begin and end in dinucleotide (5'-TG ... CA-3') inverted repeats (Voytas and Boeke 2002).
LTRs play a role in the transposition process and life cycle of retroelements; they contain regulatory elements such as "enhancers" and "promoters" capable of regulating adjacent genes present in the retroelement, and in certain cases host genes. Given that LTRs do not codify for any protein product they accumulate mutations that can be used, when comparing the nucleotide identity among LTRs of the same element to estimate the time elapsed since the integration of the LTR retroelement (San Miguel et al. 1998, Bowen and McDonald 2001; Jiang et al. 2002).
A canonical LTR displays three zones:
- An U3 region of 200-1.200 nt in size that contains the zone of promoters.
- A repeated region (R).
- An U5 region of 75-250 nt in size, which constitutes the first portion of the retrotranscribed genome.
A sequence of 18 nt in size called Primer Binding Site (PBS) is usually observed downstream to 5'LTR, the PBS is complementary to a specific zone of the 3' end of a cellular tRNA used as primer by Reverse Transcriptase to synthesize a DNA (-) chain complementary to the R-U5 zone of 5'LTR.
Another small region of ~10 A/G called "Polypurine Tract" (PPT) is also observed upstream to 3'LTR, the PPT is responsible for the beginning of the proviral DNA strand (+) synthesis (see formative process of LTRs ).
LTRs may also be found in genomes of hosts as an independent form (solo-LTRs) excised from their own retroelement. Many host genomes have a number of solo-LTRs copies that clearly exceeds the number of copies per element. This evidence has been related to both the increase of variation in size of the eukaryotic genomes and to the paradox of the "C" Value (Voytas and Boeke 1993; Lavrentieva et al. 1998; Vicient et al. 1999; Shirasu et al. 2000; Kalendar et al. 2000; Artamonova et al. 2000; Kurdyukov et al. 2001; Gao et al. 2004).
TIRs
The Terminal Inverted Repeats (TIRs) are essential for the transposition of most transposons. TIRs sequences contain DNA-binding sites that are recognized by the Transposase to form the synaptic protein-DNA complex and thus facilitating the cleavage at both strands and the subsequent transposon release (Craig et al. 2002).
Depending on the transposon family, TIRs can vary in sequence length and TR-binding site numbers and patterns, but as a first approximation, TIRs sequences can often be divided in two functional modules or domains (Szabó et al. 2010; Craig et al. 2002). The first domain includes two or three terminal base pairs and is involved in DNA cleavage and strand transfer reactions. The second domain uses to be an internal sequence in the TIR and is required for TR specific recognition and binding.