Deficiências no mundo do RNA

sexta-feira, fevereiro 14, 2020

Chemistry World


Flaws in the RNA world


Self-replicating RNA may lack the fidelity needed to originate life

Source/Fonte: © Getty Images & © Shutterstock

Look at the reliability of replication to draw conclusions on whether life emerged from an RNA world

The hypothesis of an ‘RNA world’ as the font of all life on Earth has been with us now for more than 30 years, the term having been coined by the biologist Wally Gilbert in 1986. You could be forgiven for thinking that it pretty much solves the conundrum of how the replication of DNA could have avoided a chicken-and-egg impasse: DNA replication requires protein enzymes, but proteins must be encoded in DNA. The intermediary RNA breaks that cycle of dependence because it can both encode genetic information and act catalytically like enzymes. Catalytic RNAs, known as ribozymes, play several roles in cells.

It’s an alluring picture – catalytic RNAs appear by chance on the early Earth as molecular replicators that gradually evolve into complex molecules capable of encoding proteins, metabolic systems and ultimately DNA. But it’s almost certainly wrong. For even an RNA-based replication process needs energy: it can’t shelve metabolism until later. And although relatively simple self-copying ribozymes have been made,1 they typically work only if provided with just the right oligonucleotide components to work on. What’s more, sustained cycles of replication and proliferation require special conditions to ensure that RNA templates can be separated from copies made on them.

In the soup

Perhaps the biggest problem is that self-replicating ribozymes are highly complex molecules that seem very unlikely to have randomly polymerised in a prebiotic soup. And the argument that they might have been delivered by molecular evolution merely puts the cart before the horse. The problem is all the harder once you acknowledge what a complex mess of chemicals any plausible prebiotic soup would have been. It’s nigh impossible to see how anything lifelike could come from it without mechanisms for both concentrating and segregating prebiotic molecules – to give RNA-making ribozymes any hope of copying themselves rather than just churning out junk, for example.

In short, once you look at it closely, the RNA world raises as many questions as it answers. Even one of its chief advocates, Gerald Joyce of the Scripps Research Institute in California, suggested recently that it might be necessary to consider that the RNA world was preceded by ‘some other replicating, evolving molecule’ such as peptide-nucleic acid hybrids.2 That, of course, may simply defer some of the problems rather than solving them.

Joyce and his coworkers have now found a ribozyme that holds the potential to copy heritable ‘pre-genetic’ information into RNAs considerably more complex and structured than any seen before.3 This molecule was found through a process of in vitro evolution, the criterion for selection in each round being the ability to keep adding individual nucleotides to a ‘primer’ RNA segment to make long strands – that is, to act as an RNA polymerase.

Joyce and colleagues started with a known ribozyme called the class I ligase (which links nucleotide fragments together). After 14 rounds of evolution, their best performing ribozyme was capable of joining nucleotides into three separate RNAs that would then spontaneously assemble (after purification) into the original ligase. In other words, it was capable of synthesising the RNA molecule from which it was derived – to make its own ancestor. Joyce and colleagues say this is ‘the most complex functional RNA that has been synthesized by a ribozyme’ from single nucleotides, and believe that, with further in vitro evolution, they might obtain a ribozyme of similar complexity that is genuinely able to make itself.

READ MORE HERE: Chemistry World