Byte Size Biology

This has been a topic of discussion since I was in grad school: when will the Nobel prize for the structure of the ribosome be finally awarded? Well, it finally has. Ada Yonath, Thomas Steitz and Venkatraman Ramakrishnan received the Nobel for work that has spanned three decades and an equal number of continents.

First, a victory dance:

Next, the scientific background:

And part of Ada Yonath’s model in this clip:

In the latter epoch of those  2 billion-odd years between non-life and life on early Earth, our ancestral molecular replicators were quite probably RNA, not DNA. There are many arguments for this RNA world hypothesis: RNA can store information in its sequence, and self -duplicate; it can also catalyze reactions as a ribozyme. So technically, RNA has all the facilities necessary to be a replicator. Not only that, RNA can catalyze the formation of peptide bonds, providing a plausible link between the RNA world and the protein world we live in today. One strong supporting evidence for the RNA world is the ribosome: the ubiquitous ribozyme / protein complex that translates messenger RNA to proteins. The ribosome is mostly composed of RNA, it exists in all three super-kingdoms of life, and is conserved within the super-kingdoms. But the ribosome is a very complex machine: can we find one of the ribosome’s less complex precursors?  One that post-dates the RNA-only world, but not quite as complex and specific as today’s ribosome?

Isabella Moll’s group at the Max F. Perutz Laboratories (MFPL) in Vienna may have just discovered a candidate for an ancestral ribosome.  In bacteria, messenger RNA or mRNA has a 5` untranslated region, that commonly includes the Shine-Dalgarno sequence: a six nucelotide consensus sequence AGGAGG located just before the AUG codon, which marks the translation start site. However some mRNA molecules lack a Shine- Dalgarno, yet still get translated.  Moll’s group were looking at such leaderless messenger RNA, or lmRNA. lmRNA might be a remnant dating back to a more primitive era of translation, where the Shine Dalgarno motif has not yet evolved.

Credit: Byte Size Biology

Moll’s group were using kasugamycin, an antibiotic that blocks transcription, to inhibit the translation of mRNA. While the translation of mRNA containing Shine-Dalgarno sequences was inhibited by kasugamycin, translation of lmRNA was not inhibited. When they examined the ribosomal particles that were translating lmRNA despite the presence of kasugamycin, they found their molecular weight to be lighter: 61S instead of the usual 70S in bacteria. The ribosome is a complex piece of molecular machinery, consisting of many RNA and protein components. Nevertheless, Moll’s group has shown that the smaller ribosome, lacking in many parts, can still translate lmRNA,  but not leadered (Shine-Dalgarno containing) RNA.  This “bare-bones” ribosome may very well be a version of the proto-ribosome, dating back to the dawn of life, before the separation of life’s superkingdoms.