Transcription and Translation

All Your Ribosomes Belong to Us

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So more than a week has gone by and there has been little press about the science Nobels. And I must say that this year’s Medicine and Chemistry prizes are some of the most important in quite a while. But even between the two, the Chemistry is especially important.

Why? I’m not sure. Maybe they were overshadowed by Obama’s award??? Or maybe science journalists are sleeping on the job.

I can hear them now “Ribosomes … boring.”

Nothing could be further from the truth.

Ribosomes are arguably the most important biological molecule that we know of. I don’t have much time to write long essays on the subject so I’ll just throw some ideas at you.

- The ribosome is the only known enzyme that can produce new proteins.

- Every cell has ribosomes. And I mean EVERY cell – from the lowliest bacterium to the sperm of the blue whale.

- Of all the biological molecules, ribosomes are probably the oldest. If life is 4 billion years old, it is likely that ribosomes originated that long ago.

- Like all ancient biomolecules, ribosomes are RNA enzymes. All the catalytic properties of the ribosome can be found within its rRNA, and of all ribosomal genes, these are the most conserved. In fact the ribosomal RNA gene is the most conserved of all known genes. Want to look at the next oldest genes? A lot of those ancient genes encode proteins that interact with the ribosome.

- Most Many antibiotics target bacterial ribosomes. So every time you are prescribed some medicine for that pneumonia or staph infection you are waging ribosomal warfare.

- Ribosomes are some of the most abundant molecules in your body. It has been estimated that in some cells, there is 10 times more ribosomal RNA than there is DNA.

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- Ribosomal biogenesis (the construction of new ribosomes) is extremely complicated. In eukaryotes, this process involves hundred of genes and takes place in numerous subcellular compartments. One location where much of the action occurs is the nucleolus – a dense ball found inside of the nucleus that is filled with RNA binding proteins. In this micrograph on the right, if the mouse cells’ nuclei look like small cookies, the nucleoli would be the chocolate chips. You’ll also notice that one of the nucleoli is heart shaped (that one is dedicated to you Bil!)

- Although messenger RNA is produced by RNA Polymerase II, ribosomal RNA is made by its very own enzyme, RNA Polymerase I. In a typical cell there is much far more rRNA than mRNA.

- Ribosomal proteins are some of the most abundant proteins in the cell. They are also weird. Take Budding yeast. Only 5% of that critter’s genes have introns. But almost every single ribosomal protein has one! Why? We don’t know. But since the cell spends so much time and effort making ribosomal proteins about 50% of the mRNAs produced in the typical yeast cell have introns that have to be spliced out. It’s all a big mystery.

- Ribosomes are deeply tied in with cancer. How does that work? A new view that has come out of cell biology is that making ribosomes may be a key event that regulates when cells divide. Think about it. Every time your cells grow and split into two, they must not only duplicate their DNA, but also their ribosomes. But it gets weirder – ribosomes are crucial for making … ribosomal proteins which are an essential part of ribosomes. So in some way ribosomes are partially responsible for their own duplication. In fact in a rapidly dividing cell, a ribosome can spend more than 50% of its time making ribosomal proteins. If you are a new cell and you didn’t inherit enough ribosomes from your mother cell, then your ability to produce new ribosomes for your daughter cells is impaired. Well it turns out that there is a system that regulates how and when ribosomes are made – this is called TOR signaling. This signaling network measures the amount of nutrients, energy, growth signals and determines whether the cell should make new ribosomes and when the cell should divide.

It is likely that when TOR senses that
1) there are enough nutrients
2) when energy stores are adequate and
3) when the cell has enough ribosomes,
it initiates a round of cell division.

So what happens when TOR signaling is screwed up? One outcome is that you don’t make enough ribosomes before the cell division orders are given out and the resulting cells are small. BTW if you think that this TOR signaling is some esoteric process, most of the nastiest oncogenes and many of the important tumor suppressor genes are integral parts of TOR signaling. And as you could have guessed, proteins within the TOR signaling cascade are produced from some of the oldest signaling genes in the genome.

The day that the Nobel was given for the structure of the ribosome, I told my wife that we are all ribosome monsters. Deep down all of our most ancient features are there to serve ribosomes. All the other stuff inside of cells – can be seen as nothing more than support for ribosomes so that they can duplicate themselves. In fact, from the gene centric view of life, ribosomes are by far the most spectacular replicating entities on the planet. They are in every living cell. They are more numerous and more conserved than any other gene product. They have more genes supporting their function than any other biomolecule (there are over 500 tRNA genes in the human genome!!!!) And they are indispensable to live as we know it. If you tried to design a cell from scratch and you had to come up with the ribosome …. good luck.

For other odes and dedications directed to the ribosome, visit the RNA Underworld.

Comments

  1. #1 Comrade PhysioProf
    October 15, 2009

    Dude, I really don’t think Tom needs your help explaining how his Nobel Prize is the bestest most importantest Nobel Prize EVER!

  2. #2 ponderingfool
    October 15, 2009

    - Of all the biological molecules, ribosomes are probably the oldest. If life is 4 billion years old, it is likely that ribosomes originated that long ago.
    ***************

    Why over tRNAs?

  3. #3 Alex Palazzo
    October 15, 2009

    ponderingfool,

    Sure, lump tRNAs in there too. After all, ribosomes and tRNAs need each other.

  4. #4 Alexvdb
    October 15, 2009

    Happy to see you blogging again, Alex. I always enjoy your posts.

  5. #5 Paula Helm Murray
    October 15, 2009

    this is so cool! I’m more of a taxonomic natural history amateur biologist but I find the genetic details so very interesting and cool.

    Wow

  6. #6 Paul Orwin
    October 16, 2009

    Well said, but one pedantic point (tangential) – most antibiotics target cell wall synthesis. Ribosome targeting is the next most common (there are several classes of ribosome targeting drugs, though). Something like 75% of antibiotics are beta-lactams. (this could be a bit old…)

  7. #7 Spiny Norman
    October 16, 2009

    @PP — maybe Tom and Roger should wrestle, in the style of our Greek forefathers, to settle the question of whose Nobel Prize is the bestest (my money is and always will be on FHC, dead or not).

  8. #8 Michele Arduengo
    October 16, 2009

    Great job giving perspective to the ribosome, which I think some of us take for granted because we have spent time teaching protein synthesis in first-year biology courses. Although I don’t think it’s safe to say “most” antibiotics target ribosomes, although many do and more are being developed.

  9. #9 P.Mrozek
    October 16, 2009

    As far as introns go they probably serve to control transcription. I bet transcripts containing introns have the capability to bind RNA and/or proteins and that this binding regulates the efficiency of splicing and therefore transcription. Some excised introns probably serve as signals impacting other processes including splicing of other genes forming a regulatory network.

    The simplest example of such control would be the intron reversibly binding protein/RNA encoded by the gene containing it and in that way blocking splicing and transcription. This mechanism will ensure that transcript is not produced if the product is already present in sufficient concentration. Very simple and robust way to control expression expecialy well suited to ribosomal genes since both genes and their products are present in the nucleoli.

  10. #10 Alex Palazzo
    October 16, 2009

    P.Mrozek,

    It is true that in “higher eukaryotes” the spliceosome deposits factors onto the processed mRNA. These factors are deposited on exons and thus remain on the mRNA even after processing are complete. Two such complexes are the TREX complex, which promotes nuclear export, and the Exon-Junction Complex, which helps with quality control and enhances translation. Having said all that it is not clear that any of this is happenning in yeast. In fact in our cells the highest expressed genes (histone genes) are intronless. So it is still a mystery why some histone genes are intronless in most organisms while ribosomal genes tend to have introns, even when all other genes become intronless.

  11. #11 JohnV
    October 16, 2009

    After our first rna-sequencing experiment, I’d like to voice my absolute hatred for the ribosome. As if the fact that most of the RNA in a cell is rRNA isn’t a big enough pain in the ass (coupled with 2 rounds of rRNA subtraction failing to specifically remove rRNA), the stupid protein subunits that make up the ribosome soaked up most of sequencing hits.

  12. #12 Alex Palazzo
    October 16, 2009

    Ribosomes 1: JohnV 0

  13. #13 JohnV
    October 16, 2009

    On the plus side, we have really really really deep sequence validation of the 16s and 23s rRNA sequences (~50,000x coverage).

    @$%@ ribosomes.

  14. #14 BTM
    October 16, 2009

    In bacteria a lot of ribosomal protein mRNA is actually regulated by the ribosomal proteins. Could the intron thing be a feedback loop related to that?

    Woohoo btw! Stockholm here I come.

  15. #15 Alex Palazzo
    October 16, 2009

    Congrats Bil. (For those of you who don’t know, Bil aka BTM was a co-first author on one of the ribosome structure papers.) I’m sure that with you in the ring, the Nobel greco-roman wrestling match would be over in seconds.

  16. #16 kablamo
    October 16, 2009

    Don’t forget the exciting link between TOR, translation, and aging. With rapamycin extending lifespan in mice.

  17. #17 Magpie
    October 16, 2009

    All your Ribosomes ARE belong to us.

    lrn2meme :P

    …but good post. Just the sort of thing I visit Scienceblogs to enjoy. Would read again.

  18. #18 Eric Suh
    October 18, 2009

    Great post! I have one objection, though:

    “The ribosome is the only known enzyme that can produce new proteins.”

    I guess that’s technically true (depending on your definition of “protein”), but other non-ribosomal enzymes can make polypeptides of non-trivial length (e.g. most polypeptide toxins and antibiotics).

  19. #19 kevin.
    October 18, 2009

    Booo-ring.