Monday, April 28, 2014

Tricksey Transposons

Three weeks until quals.. It is sneaking up so quickly! I am feeling completely unprepared and panicked. I am almost done with my first read (making notes from every page of the assigned reading list). The last topic is transposition! So I figured I'd combine studying with blogging tonight and bring you the featured topic of the day.

Transposons are mobile DNA elements found within genomes of all organisms ranging from the simple, like bacteria, to complex, humans for example. They can literally jump to a new spot in the genome! Transposons make up half of the human genome and are considered to be the major force driving mutations. Transposons are divided into families based on their movement mechanics and we'll take a quick look at the three types: DNA transposons, virus-like retrotransposons ad poly-A retrotransposons. 

DNA transposons are composed of target-sites and terminal inverted repeats flanking the transposable element which often contains genes that participate it's movement. In the following diagram, XX will represent the target sites, > < will represent the terminal inverted repeats and e will be the element.

XX>eeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee<XX

Within the element is often a gene to encode transposase, the enzyme responsible for moving the transposon around. DNA transposons are moved via cut and paste. The transposase binds to the terminal inverted repeats, bends the DNA so that these sequences line up and snips it out. Then it snips the target DNA and inserts the transposon element without expending any cellular energy. Now the genome has changed in 2 places. The original location of the transposon now has a deletion in it and the target now has an inserted transposon. You can imagine how this might impact the organism.. it could remove an important section of the gene, it could drop an element into a gene and make it nonfunctional or it could have no impact whatsoever.

Virus-like retrotransposons are organized with two long terminal repeat regions, that contain the target-site and terminal inverted repeats similar to DNA transposons, surrounding 2 genes: one for integrase and one for reverse transcriptase. To diagram this we will use L for the long terminal repeats (with X and > < inserted), I for integrase and R for reverse transcriptase:

LLXX>LLLLLLLLiiiiiiiiiiiiiiiiiiiiiiiiiirrrrrrrrrrrrrrrrrrrrrrLLLLLLLLLL<XXLL

Reverse transcriptase is an important and unique enzyme that runs backwards from the central dogma of genetics. Reverse transcriptase can change an RNA strand into a DNA, they go backwards and thus are "retro." When a retrotransposon is trascribed, the RNA is recognized by reverse transcriptase and turned into a special type of DNA called cDNA. Integrase targets cDNA and integrates it into the new target site of the genome. Since the original retrotransposon is not removed, simply transcribed into RNA and then changed into DNA and integrated into a new location in the genome this can be thought of a copy and paste method.

Poly-A retrotransposons, are the last major family of transposons. Unlike the previous two families, Poly-A retrotransposns do not have terminal inverted repeats. Instead the target-sites flank a 5' UTR at one end and a 3' UTR which has a lot of A's (adenine, one of the 4 nucleic acids that make up DNA) after it on the other. Inside the UTR are 2 protein encoding ORF's. To diagram these, XX still is the target site sequence, 5 will be the 5' UTR, 3 the 3' UTR, and 1, 2 for the OFRs.

XX5555555555111111111111112222222222222333333333AAAAAAAAAAAAXX

The presence of the 5' and 3' UTR, plus the repeating A sequence, makes poly-A retrotransposons appear gene-like. They move in a similar fashion to genes. The DNA is transcribed into RNA which is then translated and produces its two proteins. These proteins then bind to the RNA and move back into the nucleus. The protein-RNA combo binds to the target DNA, snips it and uses the poly-A sequence to attach to the DNA. A reverse transcriptase function of the protein then creates new DNA based on the RNA which is attached to the genome. A few fancy steps later, the RNA is degraded and the brand new DNA has been inserted.

So take home message: Genomes can be rearranged spontaneously via transposons. There are 3 types. DNA transposons jump via  cut and paste method. Retrotransposons move via an RNA intermediate in a copy and past method. Poly-A retrotransposons more closely resemble genes with their asymmetric ends and move via an RNA intermediate in a copy and paste method.

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