The RNA world strikes again (it never stopped)

Jpx is a long (over 200 nucleotides) nonCoding (for protein that is) RNA (e.g. a lncRNA).  It is an example of the RNA world from which we (presumably) sprang. One of its function is to control another RNA, and a fairly important one at that — namely Xist, which inactivates one of a woman’s two X chromosomes.  The jpx gene is just 10 kiloBases away from that of Xist. Jpx turns on the transcription of Xist which then goes and coats the X chromosome from which it is transcribed, shutting off most of its genes.

One of the mechanisms by which Jpx turns on Xist production is by binding to a protein called CTCF.  CTCF sits on the promoter of the Xist gene until Jpx binds to it displacing CTCF from the promoter.

CTCF is a much better known actor, and along with cohesin is thought to be responsible for the formation of chromosome loops, and the establishment of TADs (topologically associated domains) which are basically loops of chromosomes containing about a million nucleotides with an average of 8 protein coding genes which are coordinately expressed as a result.

That’s fairly impressive.  What happens when you knock out the jpx gene.  [ Cell vol. 184 pp. 6157 – 6173 ’21 ] did just this and all Hell broke loose.  Jpx keeps CTCF from binding promotors, and without jpx thousands of chromosome loops are replaced by others, with downregulation of some 700 protein coding genes.

Again, the RNA world is like some legacy software (think DOS) underlying the latest stuff (think Windows), forgotten but not gone.

The RNA world strikes again

Life is said to have originated in the RNA world.  We all know about the big 3 important RNAs for the cell, mRNA, ribosomal RNA and transfer RNA.  But just like the water, sewer, power and subway systems under Manhattan, there is another world down there in the cell which is just beginning to come into focus

I’ve written several posts about the RNA world in our cells (links at the end), but the latest is really staggering, in that RNA is helping to organize the how our DNA lies in the nucleus.

As usual the discoveries depended new technologies — RD-SPRITE in this case (you don’t want to know what the acronym stands for (by the bye have you noticed how many more acronyms are appearing in papers you read?).  It is extremely complex, but the technique is said to be able to simultaneously map thousands of  RNA and DNA molecules at high resolution relative to all other RNA and DNA molecules.  Details in Cell vol. 184 pp. 5775 – 5790 ’21 .

The count of long nonCoding (for protein that is) RNAs is now in the tens of thousands [ Science vol. 373 pp. 623 – 624 ’21 ]. They have all sorts of functions, but the present work shows that 93% of them stay close to the gene that transcribes them in the nucleus.  Here they bind other proteins in precise territories in the nucleus (because the gene for lncRNAs are found in territories as precise  in the nucleus).   This establishes functional compartments in the nucleus to regulate gene expression.

Interestingly long nonCoding RNAs are transcribed at very low levels, which led people to dismiss them as chaff.  By binding proteins this explains how so few molecules can do so much.

That’s pretty abstract.  Consider Xist, a large nonCoding RNA which inactivates one of the X chromosomes in females.  Just two xists are able to seed a multiprotein cloud around the Xist locus on the X.

Later to be described is Jpx which is crucial in establishing TADs (topologically associated domains)

Here are some older posts on the RNA world

Forgotten but not gone

Forgotten but not gone — take II

Forgotten but not gone — take III