Posted by So Ive been over the basics of ERVs (Intro, gag, pol, env), but Im still missing a ‘basic’ aspect of ERVs, even though I talk about them all the friggen time on this blag: LTRs.
In exogenous retroviruses, LTRs act as promoters. Genome has all the genes (gag, pol, env), LTRs make sure they, and genomic RNA, is made. But just as a side-effect of the reverse transcription process, every integrated retrovirus (provirus) has two identical LTRs, U3-R-U5. A viral genome just has an R-U5 on the 5′ end, and a U3-R on the 3′ end.
So, two promoters– One at the 5′ end, making virus, and one at the 3′ end… making… ?
This is one of the ways that retroviruses can cause cancer. Just due to chance, the retrovirus inserts just upstream of an oncogene. Throw an active promoter upstream, you get cancer. Ek.
Well, when dealing with ERVs, obviously ERV LTRs 5′ of an oncogene would be detrimental, thus not passed on.
But that doesnt mean that ERV LTRs arent contributing at all to gene expression. Assuming an ERV plops down upstream of a random gene, the LTR could:
- Be silenced epigenetically, or through mutations– nothing happens
- Provide an alternative promoter for, up/down regulating gene expression, tissue specificity
- Provide an alternative start site, creating an isoform of coded protein, or an alternative ORF
These little variations endogenous LRTs cause, in protein structure or protein expression, could be a huge driving force behind speciation and diversity! (microRNAs have a role in this too!)
Well, weve got a minor problem trying to address the impact of LTRs on gene expression in humans. We do, like, these huge data mining experiments which tell us “OMG LIEK THEIR ALL ACTIVE!”… but then you have to go back by hand to figure out whether the LTR activity is random noise, a minor contributor to gene expression, creating an alternative protein, or the sole promoter for the gene.
A review was just published that consolidates a lot of what we know about ERV LTRs and human genes.
Endogenous retroviral LTRs as promoters for human genes: A critical assessment.
Available data suggest that, while new expression patterns can arise as a result of LTR usage, this situation is relatively rare and is largely restricted to the placenta. In many cases, the LTR appears to be a minor, alternative promoter with an expression pattern similar to that of the native promoter(s) and hence likely exerts a subtle overall effect on gene expression.
AWWWWW. MAN! Bummer!
I was hoping they were gonna be all like “ERV LTRs are why humans are human and mice are mice!” That woulda been so cool!!
While there are some human genes that have totally co-opted ERV LTRs for their expression, there arent very many. And the LTRs that make alternative promoters are pretty minor. Man.
Alas, just like everything in science, and biology, and evolution, its just lots of little changes. Little changes that contribute towards big differences. Nothings the superstar.
July 16, 2009
July 16, 2009
I’m just glad I got to work in that lab while there were still some cool examples to play with.
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