Is Ribosome the New 42?

Published online at Lab Times.

Some 3.5 billion years ago, the first organisms embraced life on planet earth. A primitive envelope girded a primitive genome to make the simplest living cell. But could a loner genome account for all the complexity of the living cell – survival, sustenance and procreation?

B0006575 Molecular model of a ribosome
What is the bare minimum needed to build and sustain a living cell? Is it the genes that encode life or the fuel that powers the cell? According to Danish scientists Meredith Root-Bernstein and her father Prof. Robert Root-Bernstein, either answer may only be partly correct. But instead, a new solution to life, if not to universe and everything, may in fact be the ribosome.

 

To disentangle the complexity of life, scientists have traced back evolution and in the past decade, reconstructed the trees of life using the vast arrays of genetic data. The results foster the idea that all life-forms descended from a universal common ancestor (UCA). The UCA is a simple, hypothetical one-cell living entity, of 3.5 billion years ago, capable of most of the basic biological processes of today’s complex living organisms.

As simple as it was, the UCA is believed to have been jolted to life from a bunch of chemical molecules. For the believers of the ‘RNA-first’ theory, this was a self-copying piece of RNA – the primitive genome – that encoded life, while for those who profess a ‘metabolism-first’ model, it was a set of proteins that laid the cell’s architecture and fueled it. But neither RNA nor proteins can independently explain how simple replicable molecules evolved into complex cells with organized sub-structures capable of driving life. A new study by the father-daughter duo suggests that the ribosome could have been the best intermediate in the evolutionary jump from RNA to a cell.

B0006575 Molecular model of a ribosome

Molecular model of a ribosome. Image by Nobel laureate Venki Ramakrishnan.

Ribosomes are tiny factories in the cell where proteins are made, based on the letters of the genetic code, in a process called translation. They consist of three types of RNA (ribosomal RNA or rRNA) – 23S, 16S and 5S in bacteria – and proteins. Ribosomes are thought to serve a rather limited role of spewing out proteins but the fact that they contain both RNA and proteins make them the likely missing link between RNA and the cell. Meredith explains, “But to fill the gap, primitive ribosomes would have to be able to carry out a number of functions that are not currently attributed to them. Most importantly, these primitive ribosomes would have to be able to replicate themselves – and that means not just their RNA, but also their proteins. A self-replicating ribosome becomes something significantly more complicated than a gene, yet significantly simpler than a cell and thus a perfect missing link”.

If primitive ribosomes were self-replicating, they had to be able to autonomously copy their RNA (transcription) and make their own proteins. This could be possible only if the elements of transcription and translation were all encoded within the rRNAs. Further, the remnants of such coding should still reside in the ribosomes of present-day organisms. Meredith and Prof. Root-Bernstein began their hunt for these ‘living fossils’ in the rRNA of an E.coli strain. In addition to rRNA, protein translation also requires messenger RNAs (mRNA) and twenty transfer RNAs (tRNA) – one for each amino-acid – to decrypt the genetic code and load the appropriate amino-acid to a growing string of protein. The duo found traces of E.coli tRNA and mRNA sequences in the bacterial rRNAs suggesting that vestiges of translation are embedded in these rRNAs. All twenty tRNAs share 50-70% sequence identity with the rRNAs. The tRNAs are encoded either directly in the 16S rRNA, in which case they could be generated by simply cutting the rRNA, or indirectly in a complementary sequence in the 23S rRNA. Many of these remnant stretches even seemed capable of folding into the correct 3D structure for tRNAs – a feature crucial to tRNA function – when the sequences were modeled in 3D using a structure design algorithm.

What’s more, the team found evidence of a very minimal toolbox of proteins in the rRNAs when they aligned mRNA sequences of ‘ribosome-related’ proteins with the rRNA sequences. Gene sequences for enzymes which load tRNAs with amino acids before translation, transcriptional and translational proteins, as well as for proteins which make ATP, the energy currency of the cell, are all encrypted within the rRNAs. The mRNA and rRNA sequences matched by at least 50% and much of the similarity, where functional data was available, was found within regions that make ‘active sites’, the protein parts that define their function. “The existence of this information means that we have to rethink the divisions we make between messenger RNA, transfer RNA and ribosomal RNA – at one time, we propose, they were all integrated into the same molecule”, Meredith remarks.

Their study lends a new perspective to the origin of cells. Unlike a ‘genes-first’ and ‘metabolism-first’ theories, theirs suggests that genes and metabolism co-evolved in a primitive ribosome that could efficiently self-replicate. Meredith explains, “Looking backwards, we are hypothesizing that the RNA subunits that evolved into ribosomes would have encoded protein sub-units to which they would also have bound, thereby producing stable, functional RNA-protein structures. These functional RNA-protein structures would have been integrated later to form the ribosome. Looking forwards, we have predicted that if ribosomal RNA encodes the tRNAs and proteins necessary to carry out its own replication, then these ribosomal RNA “genes” would have formed the basis of the cellular genome as well”.

Though the study makes a more convincing claim about the origin of life than previous theories, it is restricted by a lack of resources, for instance, of functional information which was available only for a fraction of the proteins. Besides, sequence similarities does not necessarily mean that primordial rRNAs actively played the roles of mRNAs and tRNAs. “Our current study focuses mainly on the ribosomal RNA of E. coli K12…this work obviously needs to be done in detail. We would like to explore whether the protein subunits encoded by ribosomal RNA contain residual ribosomal functions and whether the transfer RNAs encoded by the ribosomal RNA can function as tRNAs”, Meredith concludes.

Photo courtesy: Wellcome Images via Creative Commons

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