New Research Reveals the Secret Behind a Key Cellular Process

The research, published online by the journal Science today, November 26, 2020, determined that instead of attaching to a specific piece of RNA near the end of transcription and helping it unwind from DNA, Rho actually “hitchhikes” on RNA polymerase for the duration of transcription. Rho cooperates with other proteins to eventually coax the enzyme through a series of structural changes that end with an inactive state enabling release of the RNA.

It’s worth studying genetics just to understand what these new discoveries mean. Thanks for helping me; I’m excited to learn more.

Does anyone have an idea of how this addition would change the animated depiction of this process at 3:50. I’m curious. DNA animations by wehi.tv for Science-Art exhibition - YouTube It “hitchhikes” there and acts as an editor?

For starters, this would not fall under the heading “genetics” in any but the most vague system of classifying biological fields. I would classify this as structural biology.

I would hope not at all. The paper is about prokaryotic transcription while the animation is about eukaryotic.

There’s an animation from my field (molecular motors) that really got the IDcreationists excited. Turns out, there’s a major elision that makes it the star of the animation look much more purposeful than it really is.

Would you like to see it?

Rho is involved in stopping transcription. I wouldn’t describe that as editing.

OK. Thanks!

Is there a difference in each in how DNA is transcribed to RNA? The author of the study was suggesting this may apply to all of life; I’m assuming she thinks it may have evolved early at a cellular level. So maybe the animation still applies? Maybe I’m just very mixed up too…

Do you mean “illusion”? Yes - this sounds interesting.

The paper linked in this post says it’s more than that…? I’m just wondering how it would be described in layman’s terms. I’m still a little hazy on the process as described.

1 Like
  1. RNA polymerase needs to be able to synthesize long - very long - mRNAs.
  2. Un-engaged (free, not transcribing) RNA polymerase is needed to initiate new rounds of gene expression.
  3. Absent additional mechanisms, given 1, all RNA polymerases in a cell will be perpetually engaged in transcription.
  4. Given 3, no new transcription can begin. This means, in essence, no transcriptional regulation.

The process described in the cited paper is one mechanism by which transcription in bacteria ceases, thereby freeing up RNA polymerase for new rounds of transcription.

5 Likes

Thanks. That helps create a picture for me.

So how did everyone think it worked before?

No, I mean a simple misrepresentation that is addressed in multiple papers. I have started a new thread with it.

Rho-dependent termination, and rho-independent termination, have been known for longer than I have been in science. I am afraid I am not old enough to remember what “everyone” thought before rho was discovered.

Sorry …

1 Like

I don’t think that’s the distinction they’re making here. Maybe I’m not understanding. She’s saying there’s something new. I’m wondering if the “new” is how it controls RNA rather than just terminating it, if I’m even using the right words to explain that.

“We started studying Rho, and realized it cannot possibly work in ways people tell us it works,” said Irina Artsimovitch, co-lead author of the study and professor of microbiology at The Ohio State University.

The team used sophisticated microscopes to reveal how Rho acts on a complete transcription complex composed of RNA polymerase and two accessory proteins that travel with it throughout transcription.

“This is the first structure of a termination complex in any system, and was supposed to be impossible to obtain because it falls apart too quickly,” Artsimovitch said.

“It answers a fundamental question — transcription is fundamental to life, but if it were not controlled, nothing would work. RNA polymerase by itself has to be completely neutral. It has to be able to make any RNA, including those that are damaged or could harm the cell. While traveling with RNA polymerase, Rho can tell if the synthesized RNA is worth making — and if not, Rho releases it.”

Artsimovitch has made many important discoveries about how RNA polymerase so successfully completes transcription. She didn’t set out to counter years of understanding about Rho’s role in termination until an undergraduate student in her lab identified surprising mutations in Rho while working on a genetics project.

Rho is known to silence the expression of virulence genes in bacteria, essentially keeping them dormant until they’re needed to cause infection. But these genes do not have any RNA sequences that Rho is known to preferentially bind. Because of that, Artsimovitch said, it has never made sense that Rho looks only for specific RNA sequences, without even knowing if they are still attached to RNA polymerase.

Edit: I realized I was asking the wrong question.

I watched some videos to understand how transcription works and its much more complicated than I imagined even from the animation! I can see that since termination isn’t animated at all, my question would have been complicated to answer.

I see that this is the way that it has been understood

In every textbook, Rho is used as a model terminator that, using its very strong motor force, binds to the RNA and pulls it out of RNA polymerase.

This is what the researcher is saying it does now.

Rho cooperates with other proteins to eventually coax the enzyme through a series of structural changes that end with an inactive state enabling release of the RNA

So I understand the research as saying Rho is not binding to and traveling up the RNA, but hitchhiking on the RNA polymerase and then changing its structure to release the RNA?

We don’t say “changing its structure” in such cases, we say “causing a conformational change.”

IDcreationists (especially Doug Axe) tend to promote the false assumption that proteins have a single, fixed conformation, and that they were designed to hold that one. The reality is that thousands of proteins are on the razor’s edge between two very different conformations, each of which we call “metastable.”

A couple of systems that are better understood and illustrate this are:

  1. muscle contraction, which involves many conformational changes on millisecond scales; and
  2. Prion diseases, in which the functional protein is in a less-stable conformation than the disease-causing conformation, which is too stable and accumulates, killing the organism.
2 Likes

That’s a good description. Bear in mind that, somewhere along the way, rho actually does bind to RNA. What is of particular interest to me is that this general theme - a termination factor “hitchhiking” on the transcription complex - is seen in eukaryotes and prokaryotes alike.

The other thing that stands out for me is the use of cryo-electron microscopy to tease out atomic-level structures. Old timers would likely consider X-ray crystallography to be the gold standard when it comes to studies of 3-D structures of proteins and complexes. Cryo-EM has revolutionized the field, and made accessible to structural studies large multimeric complexes. The technique and advances it has enabled are fairly amazing.

3 Likes

Perhaps @Art could chime in here too. But my understanding was the structure / confirmation change / whatever you want to call it :slight_smile: , was to the RNA polymerase and not Rho.

The team used sophisticated microscopes to reveal how Rho acts on a complete transcription complex composed of RNA polymerase and two accessory proteins that travel with it throughout transcription.

I was getting a picture of what would be equivalent to it turning into the edge of a tape dispenser and the tape getting cut, haha, and the researcher was saying it’s amazing it doesn’t fall apart. That was just my imagination running wild… please correct any of my misunderstanding or imaginings…