Able was I ere I saw Elba said Napoleon. It’s called a palindrome, and can be read either way. So can DNA which brings me to antisense transcription of DNA, particularly in two famous retroviruses –the AIDS virus (HIV1) and HTLV-1.
Proc. Natl. Acad. Sci. vol. 118 e2014783118 ’21 shows that mRNA can moonlight to do other things than code for protein. Here’s a direct quote to set the stage.
“Retroviruses share a similar genome structure. The integrated retroviral genome, called the provirus, has two identical long terminal repeats (LTR) located at its 5′ and 3′ ends, respectively. The 5′ LTR acts as the promoter of almost all retroviral genes and thus is indispensable for viral transcription and replication. However, selective methylation of the 5′ LTR and the subsequent viral latency have been observed in HIV-1 and HTLV-1. In contrast, the 3′ LTR of HIV-1 and HTLV-1 remains nonmethylated, and recent findings have shown that novel retroviral genes are transcribed from the 3′ LTR in an antisense direction”.
The 3′ LTR of the AIDS virus enables antisense transcription for the unimaginatively named ASP (AntiSense Protein). So the mRNA for ASP is transcribed in the nucleus. But it doesn’t get out as well as it might, because its 5′ end isn’t polyAdenylated. So it sticks around in the nucleus and binds to DNA, turning off transcription of the regular HIV1 genome — e.g. helping to maintain viral latency (and preventing a true cure of HIV1 in any individual).
This is unprecedented. Here is an mRNA with a completely different function (e.g. regulating gene expression). This is classic moonlighting as something else and the authors call the mRNA for ASP a bifunctional mRNA.
The other, retrovirus HTLV-1 also has an antisense transcript making a protein called HBZ (your don’t want to know what it stands for). Unlike ASP, HBZ turns on a variety of genes.
I’ve been fascinated by moonlighting molecules, probably because they show the depths of our ignorance of the biochemical machinations inside the cell. Even when you think you’ve got the function of a molecule tied down, it goes off and does something else.
Here are some links to other posts on the subject. To get to them just click on the titles
Moonlighting molecules
More moonlighting
A moonlighting quorum sensing molecule
Chemiotics II 