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ChristopherBell RNAworld

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Christopher Bell
The RNA world
Looking around the world it is evident that life is all interconnected, but what did it
originate from? As scientists work back through the evolutionary chain and time, life gets more
and more simple, and less and less distant. However bringing life back to a single point or
species is very difficult for a number of reasons. Firstly, that species would have to originate
from the “primordial soup” of relatively few elements that were available on this planet roughly
4 billion years ago. Secondly, the life form produced would have to be able to self replicate, and
metabolize in order to survive. Thirdly, this life form would have to have the building blocks
necessary to allow for its eventual evolution into the life forms we see on Earth today. A number
of scientists have hypothesized that all of these prerequisites could be met by the polymer RNA.
This essay will discuss the merits of this hypothesis by describing the role of RNA in modern
day cells, showing RNA’s versatility, and citing three outstanding characteristics that RNA has
which may have helped it to form and survive on this primordial world.
RNA is an essential part of all living organisms. It is fundamental in the transcription of
DNA’s genetic information, the carrying of that information to the cytoplasm, and the translation
of that information into protein. Although it is a single stranded molecule with only 4 bases, it is
extremely diverse in its functions. The traditional three types of RNAs spoken about in a biology
textbook are: mRNA for copying a strand of DNA and carrying that information to the ribosome,
tRNA which binds to amino acids and delivers them to the ribosome, and rRNA which is
foundational for ribosome formation. Each of these types of RNA is very unique and essential
for the production of proteins which carry out most of life’s processes, and each of them is
further enhanced by other RNA based enzymes such as peptidyl-transferase and aminoacyl RNA
which assist in the preparation and transferring of amino acids from tRNA to the forming
peptide. (Additionally, RNA also is essential for the formation of the spliceosome complex
(snRNPs) which removes introns from the mRNA sequence before it is translated into protein,
and RNA performs a similar function in telomerase which splices out chromosomal termini (3).
RNA can also assist in intercellular signalling and transport, nucleoporin function, as well as
gene and histone regulation. (2) Outside of Eukaryotic cells it can perform other unique
functions. In viruses for example ncRNA can help the virus to bypass a cell's outer defenses and
after entry help the virus to hijack the cells reproductive processes for its own use (3).
What gives RNA this incredible versatility? Firstly, its single stranded nature allows it to
fold itself into unique conformational and three dimensional shapes that have their own
functions. These unique shapes help the RNA in various forms of catalysis or assist in protein
synthesis. (2) In tRNA, for example, the RNA folds and binds onto itself forming what appears
to be a double stranded lower case t with specific regions allowing for the binding of an amino
acid and a codon. A second source of variation is its ability to bind to a number of metabolites
such as guanine, lysine, and S-adenosylmethionine. These factors act as RNA switches which
allow it to alter its function. For example, gram positive bacteria use this property of RNA to
assist in gene regulation. (6) RNA can also bind to several different cofactors to alter its function.
tRNA attaches to an amino acyl group which charges the tRNA and allows it to bind to its target
amino acid. A last source of variation comes from its ability to remain a single strand, unlike its
cousin DNA. This allows the RNA to serve as a signal recognizing sequence by binding to
specific regions of other RNA based molecules. As mentioned previously, the unique functions
and versatility of RNA suggest the possibility that RNA could be the ancestor from which all life
descended. While there are several compelling arguments for why this might be the case, this
paper will discuss only three.
Firstly, if RNA would provide an easy to follow continuity for the development of life.
As the saying goes, “the simplest explanation is often the best.” The three molecules that are
essential to all life are DNA, RNA, and proteins. Of the three, RNA is the simplest and therefore
the most likely. For example, the machinery required for producing RNA is used as a precursor
for DNA which requires an additional 2 enzymes to form. (3) Proteins likely require RNA
precursors. mRNA, tRNA, and rRNA all go into the synthesis of proteins. seems much more
likely that RNA would form before DNA or proteins. Furthering this continuity, RNA is well
conserved between living organisms. If all life originated from RNA, then there would be
regions of the RNA code that have similar sequence and function in all living things. For
example, promoter RNA sequences are extremely well conserved between all forms of life, often
within a few base pairs of each other. (4) Ribosomal RNA, though less conserved than promoter
sequences, still remains very similar between animals, plants, and bacteria. The same could be
said for tRNA and mRNA.
A secondary evidence supporting the RNA world is RNA’s versatility as both a catalyst
and a messenger. In order to survive, the first life form would have to be self replicating. Initially
this was a big stumbling block for RNA as no evidence had been found to suggest that RNA
could self-replicate in primordial conditions. However, in 2001 Johnston et al stated a ribozyme
catalyzed RNA replication could occur (3) and in 2002 Natasha Paul was able to prove that RNA
could perform that self replication. (1) In 2009 Powner et al demonstrated that RNA pyrimidines
could be formed in primordial conditions (3). Scientists have still been unable to do purine
synthesis, but in time this could prove a possibility. Additionally, RNA can form a ribozyme
complex that can splice out sections of DNA for translation or catalyze specific reactions that
might help in metabolic processes (2). Evidence for these processes can be seen in much of the
now unused portions of RNA by use of the SELEX program (3). Ribozyme splicing activity
would also plausibly allow for relatively rapid evolution of the molecule, and the future
formation of proteins, which shows a clear evolutionary path to what exists in the world today.
Lastly, it is plausible that RNA could form from AMP dependent cofactors which are still
closely associated with it today. Cofactors such as NADP, and FAD, have a similar structure to
RNA minus the 5’-5’ bond. However it is possible for these molecules to receive their phosphate
group on the 3’ carbon of the ribose molecule. Furthermore, studies have shown that the location
of the RNA bonds on the ribose sugar does not affect the 3D structure of the overall molecule.
(6) This suggests that it would be possible for the RNA to function even if it did not bond
properly in the initial phases of life. The formation of a possible precursor for RNA development
lends credence to an RNA world. This is further augmented by the continued association of RNA
with these cofactors.
Few possible precursors to life exist with the ability to form, survive, and reproduce in
the conditions on Earth 4 billion years ago. RNA demonstrates a continuity of evolution with the
world we see today, the ability to replicate and provide the energy necessary for its continuation,
the existence of possible precursors that could lead to its formation, as well as a simple
mechanism for its continued growth and evolution. For this reason the idea of an RNA world
which began with Francis Crick, has continued to be a predominant theory for evolutionary
biologists for over 50 years. In the past 10 years alone, evidence has come forward further
assisting the hypothesis of a spontaneously created RNA based world. Who can say what further
evidence the next 10 years might bring?
Bibliography
1. Akst, Jef. “RNA World 2.0.” The Scientist, 2014.
2. Benner, S. A., et al. “Setting the Stage: The History, Chemistry, and Geobiology behind
RNA.” Cold Spring Harbor Perspectives in Biology, vol. 4, no. 1, 2010,
doi:10.1101/cshperspect.a003541.
3. Cech, T. R. “The RNA Worlds in Context.” Cold Spring Harbor Perspectives in Biology,
vol. 4, no. 7, 2011, doi:10.1101/cshperspect.a006742.
4. Cech, Thomas R. “Crawling Out of the RNA World.” Cell, vol. 136, no. 4, 2009, pp.
599–602., doi:10.1016/j.cell.2009.02.002.
5. Robertson, Michael P, and Gerald F Joyce. “The Origins of the RNA World.” Cold
Spring Harbor Perspectives in Biology, 2012.
6. Yarus, Michael “Getting Past the RNA World.” Cold Spring Harbor Perspectives in
Biology, 2009
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