Editing RNA world (section)

== Properties of RNA ==
The properties of RNA make the idea of the RNA world hypothesis conceptually plausible, though its general acceptance as an explanation for the origin of life requires further evidence.<ref name="Atk06">{{cite book|last1=Atkins|first1=John F.|title=The RNA world: the nature of modern RNA suggests a prebiotic RNA world|last2=Gesteland|first2=Raymond F.|last3=Cech|first3=Thomas|publisher=Cold Spring Harbor Laboratory Press|year=2006|isbn=978-0-87969-739-6|location=Plainview, N.Y|name-list-style=vanc}}</ref> RNA is known to form efficient catalysts, and its similarity to DNA makes clear its ability to store information. Opinions differ, however, as to whether RNA constituted the first autonomous self-replicating system or was a derivative of a still-earlier system.<ref name= Cech2012 /> One version of the hypothesis is that a different type of [[nucleic acid]], termed ''[[#Alternative hypotheses|pre-RNA]]'', was the first one to emerge as a self-reproducing molecule, to be replaced by RNA only later. On the other hand, the discovery in 2009 that activated [[pyrimidine]] [[ribonucleotides]] can be synthesized under plausible [[Abiogenesis|prebiotic]] conditions<ref name="Powner2009">{{cite journal | vauthors = Powner MW, Gerland B, Sutherland JD | title = Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions | journal = Nature | volume = 459 | issue = 7244 | pages = 239–242 | date = May 2009 | pmid = 19444213 | doi = 10.1038/nature08013 | s2cid = 4412117 | bibcode = 2009Natur.459..239P }}</ref> suggests that it is premature to dismiss the RNA-first scenarios.<ref name= Cech2012 /> Suggestions for 'simple' ''pre-RNA'' nucleic acids have included [[peptide nucleic acid]] (PNA), [[threose nucleic acid]] (TNA) or [[glycol nucleic acid]] (GNA).<ref>{{cite journal | vauthors = Orgel L | title = Origin of life. A simpler nucleic acid | journal = Science | volume = 290 | issue = 5495 | pages = 1306–1307 | date = November 2000 | pmid = 11185405 | doi = 10.1126/science.290.5495.1306 | s2cid = 83662769 }}</ref><ref>{{cite journal | vauthors = Nelson KE, Levy M, Miller SL | title = Peptide nucleic acids rather than RNA may have been the first genetic molecule | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 8 | pages = 3868–3871 | date = April 2000 | pmid = 10760258 | pmc = 18108 | doi = 10.1073/pnas.97.8.3868 | doi-access = free | bibcode = 2000PNAS...97.3868N }}</ref> Despite their structural simplicity and possession of properties comparable with RNA, the chemically plausible generation of "simpler" nucleic acids under prebiotic conditions has yet to be demonstrated.<ref>{{cite journal | vauthors = Anastasi C, Buchet FF, Crowe MA, Parkes AL, Powner MW, Smith JM, Sutherland JD | title = RNA: prebiotic product, or biotic invention? | journal = Chemistry & Biodiversity | volume = 4 | issue = 4 | pages = 721–739 | date = April 2007 | pmid = 17443885 | doi = 10.1002/cbdv.200790060 | s2cid = 23526930 }}</ref>

=== RNA as an enzyme ===
{{Further|Ribozyme}}

In the 1980s, RNA structures capable of self-processing were discovered,<ref>{{Cite journal |last1=Kruger |first1=Kelly |last2=Grabowski |first2=Paula J. |last3=Zaug |first3=Arthur J. |last4=Sands |first4=Julie |last5=Gottschling |first5=Daniel E. |last6=Cech |first6=Thomas R. |date=November 1982 |title=Self-splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena |url=http://dx.doi.org/10.1016/0092-8674(82)90414-7 |journal=Cell |volume=31 |issue=1 |pages=147–157 |doi=10.1016/0092-8674(82)90414-7 |pmid=6297745 |s2cid=14787080 |issn=0092-8674}}</ref> with the RNA [[Moiety (chemistry)|moiety]] of [[ribonuclease P]] acting as its catalytic subunit.<ref>{{Cite journal |last1=Guerrier-Takada |first1=Cecilia |last2=Gardiner |first2=Katheleen |last3=Marsh |first3=Terry |last4=Pace |first4=Norman |last5=Altman |first5=Sidney |date=December 1983 |title=The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme |url=http://dx.doi.org/10.1016/0092-8674(83)90117-4 |journal=Cell |volume=35 |issue=3 |pages=849–857 |doi=10.1016/0092-8674(83)90117-4 |pmid=6197186 |s2cid=39111511 |issn=0092-8674}}</ref> These catalytic RNAs – referred to as [[Ribozyme|RNA enzymes]], or ribozymes – are found in today's DNA-based life and could be examples of [[living fossil]]s. Ribozymes play vital roles, such as that of the [[ribosome]]. The large subunit of the ribosome includes an [[Ribosomal RNA|rRNA]] responsible for the peptide bond-forming [[peptidyl transferase]] activity of protein synthesis. Many other ribozyme activities exist; for example, the [[hammerhead ribozyme]] performs self-cleavage<ref>{{cite journal | vauthors = Forster AC, Symons RH | title = Self-cleavage of plus and minus RNAs of a virusoid and a structural model for the active sites | journal = Cell | volume = 49 | issue = 2 | pages = 211–220 | date = April 1987 | pmid = 2436805 | doi = 10.1016/0092-8674(87)90562-9 | s2cid = 33415709 }}</ref> and an [[RNA-dependent RNA polymerase|RNA polymerase]] ribozyme can synthesize a short RNA strand from a primed RNA template.<ref>{{cite journal | vauthors = Johnston WK, Unrau PJ, Lawrence MS, Glasner ME, Bartel DP | title = RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension | journal = Science | volume = 292 | issue = 5520 | pages = 1319–1325 | date = May 2001 | pmid = 11358999 | doi = 10.1126/science.1060786 | url = http://web.wi.mit.edu/bartel/pub/publication_reprints/Johnston_Science01.pdf | url-status = live | s2cid = 14174984 | citeseerx = 10.1.1.70.5439 | bibcode = 2001Sci...292.1319J | archive-url = https://web.archive.org/web/20120227163451/http://web.wi.mit.edu/bartel/pub/publication_reprints/Johnston_Science01.pdf | archive-date = 2012-02-27 }}</ref>

Among the enzymatic properties important for the beginning of life are:
;Self-replication
:The ability to [[self-replication|self-replicate]] or synthesize other RNA molecules; relatively short RNA molecules that can synthesize others have been artificially produced in the lab. The shortest was 165 bases long, though it has been estimated that only part of the molecule was crucial for this function. One version, 189 bases long, had an error rate of just 1.1% per nucleotide when synthesizing an 11-nucleotide long RNA strand from primed template strands.<ref>{{cite journal | vauthors = Johnston WK, Unrau PJ, Lawrence MS, Glasner ME, Bartel DP | title = RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension | journal = Science | volume = 292 | issue = 5520 | pages = 1319–1325 | date = May 2001 | pmid = 11358999 | doi = 10.1126/science.1060786 | s2cid = 14174984 | citeseerx = 10.1.1.70.5439 | bibcode = 2001Sci...292.1319J }}</ref> This 189-base pair ribozyme could polymerize a template of at most 14 nucleotides in length, which is too short for self-replication, but is a potential lead for further investigation. The longest [[primer extension]] performed by a ribozyme polymerase was 20 bases.<ref name="pmid17586759">{{cite journal | vauthors = Zaher HS, Unrau PJ | title = Selection of an improved RNA polymerase ribozyme with superior extension and fidelity | journal = RNA | location = New York, N.Y. | volume = 13 | issue = 7 | pages = 1017–26 | date = July 2007 | pmid = 17586759 | pmc = 1894930 | doi = 10.1261/rna.548807 }}</ref> In 2016, researchers reported the use of in vitro evolution to improve dramatically the activity and generality of an RNA polymerase ribozyme by selecting variants that can synthesize functional RNA molecules from an RNA template.<ref name="Horning-2016" /> Each RNA polymerase ribozyme was engineered to remain linked to its new, synthesized RNA strand; this allowed the team to isolate successful polymerases. The isolated RNA polymerases were again used for another round of evolution. After several rounds of evolution, they obtained one RNA polymerase ribozyme called 24-3 that was able to copy almost any other RNA, from small catalysts to long RNA-based enzymes. Particular RNAs were amplified up to 10,000 times, a first RNA version of the [[polymerase chain reaction]] (PCR).<ref name="Horning-2016">{{cite journal | vauthors = Horning DP, Joyce GF | title = Amplification of RNA by an RNA polymerase ribozyme | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 113 | issue = 35 | pages = 9786–9791 | date = August 2016 | pmid = 27528667 | pmc = 5024611 | doi = 10.1073/pnas.1610103113 | bibcode = 2016PNAS..113.9786H | doi-access = free }}</ref>

:[[Life]] is thought to have emerged from inanimate matter more than 3.5 billion years ago when a rudimentary [[abiogenesis]] process gradually evolved into an [[autocatalysis|autocatalytic process]] capable of template-based replication.<ref name = Paavlinova2023>{{cite journal |vauthors=Pavlinova P, Lambert CN, Malaterre C, Nghe P |title=Abiogenesis through gradual evolution of autocatalysis into template-based replication |journal=FEBS Lett |volume=597 |issue=3 |pages=344–379 |date=February 2023 |pmid=36203246 |doi=10.1002/1873-3468.14507 |url=|doi-access=free }}</ref>  It was proposed on the basis of experimentally feasible [[RNA]] reactions catalyzed by a [[ribozyme]], that the emergence of life was likely a gradual process involving the evolutionary properties of [[genetic variation|variation]], [[heredity]] and [[reproduction]], ultimately allowing for [[Darwinism|Darwinian evolution]].<ref name = Paavlinova2023/>  Recent efforts have been directed at trying to demonstrate [[RNA]] replication under conditions that assume the presence during early evolution of plausible [[nucleotide]] intermediates and plausible environmental conditions that could favor strand replication alternating with strand separation.  One such effort was the demonstration of high fidelity RNA copying using 2’,3’-cyclic phosphate ligation to allow [[polynucleotide]] synthesis under conditions also compatible with strand separation.<ref>{{cite journal |vauthors=Calaça Serrão A, Wunnava S, Dass AV, Ufer L, Schwintek P, Mast CB, Braun D |title=High-Fidelity RNA Copying via 2',3'-Cyclic Phosphate Ligation |journal=J Am Chem Soc |volume=146 |issue=13 |pages=8887–8894 |date=April 2024 |pmid=38503430 |doi=10.1021/jacs.3c10813 |url=|pmc=10995993 }}</ref>  In another study, it was shown that in a model oscillating [[Hadean]] environment likely to have been abundant during early evolution, that ribozyme-mediated RNA synthesis and replication can occur.<ref>{{cite journal |vauthors=Salditt A, Karr L, Salibi E, Le Vay K, Braun D, Mutschler H |title=Ribozyme-mediated RNA synthesis and replication in a model Hadean microenvironment |journal=Nat Commun |volume=14 |issue=1 |pages=1495 |date=March 2023 |pmid=36932102 |doi=10.1038/s41467-023-37206-4 |url=|pmc=10023712 }}</ref> 
;Catalysis
:The ability to [[Catalysis|catalyze]] simple chemical reactions—which would enhance creation of molecules that are building blocks of RNA molecules (i.e., a strand of RNA that would make creating more strands of RNA easier). Relatively short RNA molecules with such abilities have been artificially formed in the lab.<ref name="pmid9831528">{{cite journal | vauthors = Huang F, Yang Z, Yarus M |authorlink3=Michael Yarus| title = RNA enzymes with two small-molecule substrates | journal = Chemistry & Biology | volume = 5 | issue = 11 | pages = 669–678 | date = November 1998 | pmid = 9831528 | doi = 10.1016/s1074-5521(98)90294-0 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Unrau PJ, Bartel DP | title = RNA-catalysed nucleotide synthesis | journal = Nature | volume = 395 | issue = 6699 | pages = 260–263 | date = September 1998 | pmid = 9751052 | doi = 10.1038/26193 | s2cid = 9734076 | bibcode = 1998Natur.395..260U }}</ref> A recent study showed that almost any nucleic acid can evolve into a catalytic sequence under appropriate selection. For instance, an arbitrarily chosen 50-nucleotide DNA fragment encoding for the ''[[Taurine cattle|Bos taurus]]'' (cattle) [[albumin]] mRNA was subjected to test-tube evolution to derive a catalytic DNA (a [[deoxyribozyme]], also called a DNAzyme) with RNA-cleavage activity. After only a few weeks, a DNAzyme with significant catalytic activity had evolved.<ref name="Gysbers">{{cite journal | vauthors = Gysbers R, Tram K, Gu J, Li Y | title = Evolution of an Enzyme from a Noncatalytic Nucleic Acid Sequence | journal = Scientific Reports | volume = 5 | pages = 11405 | date = June 2015 | pmid = 26091540 | pmc = 4473686 | doi = 10.1038/srep11405 | bibcode = 2015NatSR...511405G }}</ref> In general, DNA is much more chemically inert than RNA and hence much more resistant to obtaining catalytic properties. If in vitro evolution works for DNA it will happen much more easily with RNA. In 2022, Nick Lane and coauthors showed in a computational simulation that short RNA sequences could have been capable of catalyzing {{CO2}} fixation which supported protocell replication and growth.<ref>{{cite journal | vauthors = Nunes Palmeira R, Colnaghi M, Harrison SA, Pomiankowski A, Lane N | title = The limits of metabolic heredity in protocells | journal = Proceedings. Biological Sciences | volume = 289 | issue = 1986 | pages = 20221469 | date = November 2022 | pmid = 36350219 | pmc = 9653231 | doi = 10.1098/rspb.2022.1469 }}</ref>
;Amino acid-RNA ligation
:The ability to conjugate an amino acid to the 3'-end of an RNA in order to use its chemical groups or provide a long-branched [[aliphatic]] sidechain.<ref name="pmid21779963">{{cite journal | vauthors = Erives A | title = A model of proto-anti-codon RNA enzymes requiring L-amino acid homochirality | journal = Journal of Molecular Evolution | volume = 73 | issue = 1–2 | pages = 10–22 | date = August 2011 | pmid = 21779963 | pmc = 3223571 | doi = 10.1007/s00239-011-9453-4 | bibcode = 2011JMolE..73...10E }}</ref>
;Peptide bond formation
:The ability to catalyse the formation of [[peptide bonds]] between amino acids to produce short [[peptide]]s or longer [[protein]]s. This is done in modern cells by ribosomes, a complex of several RNA molecules known as [[rRNA]] together with many proteins. The rRNA molecules are thought responsible for its enzymatic activity, as no amino-acid residues lie within 18[[Ångström|Å]] of the enzyme's [[active site]],<ref name="Atk06" /> and, when the majority of the amino-acid residues in the ribosome were stringently removed, the resulting ribosome retained its full [[peptidyl transferase]] activity, fully able to catalyze the formation of peptide bonds between amino acids.<ref name="pmid1604315">{{cite journal | vauthors = Noller HF, Hoffarth V, Zimniak L | title = Unusual resistance of peptidyl transferase to protein extraction procedures | journal = Science | volume = 256 | issue = 5062 | pages = 1416–1419 | date = June 1992 | pmid = 1604315 | doi = 10.1126/science.1604315 | bibcode = 1992Sci...256.1416N }}</ref> A pseudo 2 fold symmetry of the region surrounding the peptidyl transferase center led to the hypothesis of the Proto-Ribosome, that a vestige of an ancient dimeric molecule from the RNA world is functioning within the ribosome.<ref name="pmid21930590">{{cite journal | vauthors = Krupkin M, Matzov D, Tang H, Metz M, Kalaora R, Belousoff MJ, Zimmerman E, Bashan A, Yonath A | display-authors = 6 | title = A vestige of a prebiotic bonding machine is functioning within the contemporary ribosome | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 366 | issue = 1580 | pages = 2972–2978 | date = October 2011 | pmid = 21930590 | pmc = 3158926 | doi = 10.1098/rstb.2011.0146 | doi-access = free }}</ref> An RNA molecule with the ribosomal RNA sequence has been synthesized in the lab to test the Proto-ribosome hypothesis and was able to dimerize and to form peptide bonds.<ref name="pmid35137169">{{cite journal | vauthors = Bose T, Fridkin G, Davidovich C, Krupkin M, Dinger N, Falkovich AH, Peleg Y, Agmon I, Bashan A, Yonath A | display-authors = 6 | title = Origin of life: protoribosome forms peptide bonds and links RNA and protein dominated worlds | journal = Nucleic Acids Research | volume = 50 | issue = 4 | pages = 1815–1828 | date = February 2022 | pmid = 35137169 | pmc = 8886871 | doi = 10.1093/nar/gkac052 | doi-access = free }}</ref> A much shorter RNA molecule has been synthesized in the laboratory with the ability to form [[peptide bonds]], and it has been suggested that rRNA has evolved from a similar molecule.<ref>{{cite journal | vauthors = Zhang B, Cech TR | title = Peptide bond formation by in vitro selected ribozymes | journal = Nature | volume = 390 | issue = 6655 | pages = 96–100 | date = November 1997 | pmid = 9363898 | doi = 10.1038/36375 | s2cid = 4398830 | bibcode = 1997Natur.390...96Z }}</ref> It has also been suggested that amino acids may have initially been involved with RNA molecules as cofactors enhancing or diversifying their enzymatic capabilities, before evolving into more complex peptides. Similarly, [[tRNA]] is suggested to have evolved from RNA molecules that began to catalyze amino acid transfer.<ref>{{cite journal | vauthors = Szathmáry E | title = The origin of the genetic code: amino acids as cofactors in an RNA world | journal = Trends in Genetics | volume = 15 | issue = 6 | pages = 223–229 | date = June 1999 | pmid = 10354582 | doi = 10.1016/S0168-9525(99)01730-8 }}</ref>

==== Cofactors ====
:Protein enzymes catalyze various chemical reactions, but over half of them incorporate cofactors to facilitate and diversify their catalytic activities.<ref>{{Cite journal |last=Decker |first=Karl |date=2006-01-17 |title=The Pyridine Nucleotide Coenzymes. Herausgegeben von J. Everse, B. Anderson und K.-S. You. Academic Press, New York 1982. XXXV, 389 S., geb. $ 46.00 |url=http://dx.doi.org/10.1002/ange.19830951241 |journal=Angewandte Chemie |volume=95 |issue=12 |pages=1033–1034 |doi=10.1002/ange.19830951241 |issn=0044-8249}}</ref> Cofactors are essential in biology, as they are based largely on nucleotides rather than amino acids. Ribozymes use nucleotide cofactors to create metabolism, with two basic choices: non-covalent binding or covalent attachment. Both approaches have been demonstrated using directed evolution to reinvent RNA dupes of protein-catalyzed processes. Lorsch and Szostak <ref>{{Cite journal |last1=Ekland |first1=Eric H. |last2=Szostak |first2=Jack W. |last3=Bartel |first3=David P. |date=1995-07-21 |title=Structurally Complex and Highly Active RNA Ligases Derived from Random RNA Sequences |url=http://dx.doi.org/10.1126/science.7618102 |journal=Science |volume=269 |issue=5222 |pages=364–370 |doi=10.1126/science.7618102 |pmid=7618102 |bibcode=1995Sci...269..364E |s2cid=40795082 |issn=0036-8075}}</ref> investigated ribozymes that could phosphorylate themselves and use [[Adenosine triphosphate#ATP analogues|ATP-γS]] as a substrate. However, only one of the seven classes of selected ribozymes had detectable ATP affinity, indicating that the ability to bind ATP was compromised. NAD<sup>+</sup>- dependent redox ribozymes were also evaluated.<ref>{{Cite journal |last1=Tsukiji |first1=Shinya |last2=Pattnaik |first2=Swetansu B |last3=Suga |first3=Hiroaki |date=2003-08-10 |title=An alcohol dehydrogenase ribozyme |url=http://dx.doi.org/10.1038/nsb964 |journal=Nature Structural & Molecular Biology |volume=10 |issue=9 |pages=713–717 |doi=10.1038/nsb964 |pmid=12910259 |s2cid=41081956 |issn=1545-9993}}</ref> The select ribozyme had a rate of enhancement of more than 10<sup>7</sup> fold and was proven to catalyze the reverse reaction - benzaldehyde reduction by NADH.<ref>{{Cite journal |last1=Tsukiji |first1=Shinya |last2=Pattnaik |first2=Swetansu B. |last3=Suga |first3=Hiroaki |date=2004-04-06 |title=Reduction of an Aldehyde by a NADH/Zn<sup>2+</sup>-Dependent Redox Active Ribozyme |url=http://dx.doi.org/10.1021/ja0495213 |journal=Journal of the American Chemical Society |volume=126 |issue=16 |pages=5044–5045 |doi=10.1021/ja0495213 |pmid=15099068 |issn=0002-7863}}</ref> Since the usage of adenosine as a cofactor is prevalent in current metabolism and is likely to have been common in the RNA world, these discoveries are essential for the evolution of metabolism in the RNA world.

=== RNA in information storage ===
RNA is a very similar molecule to DNA, with only two significant chemical differences (the backbone of RNA uses ribose instead of deoxyribose and its nucleobases include [[uracil]] instead of [[thymine]]). The overall structure of RNA and DNA are immensely similar—one strand of DNA and one of RNA can bind to form a double helical structure. This makes the storage of information in RNA possible in a very similar way to the storage of information in DNA. However, RNA is less stable, being more prone to hydrolysis due to the presence of a hydroxyl group at the ribose 2' position.

[[File:Ribonucleic acid chemical structure.svg|thumb|The major difference between RNA and DNA is the presence of a [[hydroxyl]] group at the 2'-position.]]

==== Comparison of DNA and RNA structure ====
{{Main|RNA|DNA}}

The major difference between RNA and DNA is the presence of a [[hydroxyl]] group at the 2'-position of the [[ribose]] sugar in RNA (illustration, right).<ref name="Atk06" /> This group makes the molecule less stable because, when not constrained in a double helix, the 2' hydroxyl can chemically attack the adjacent [[phosphodiester bond]] to cleave the phosphodiester backbone. The hydroxyl group also forces the ribose into the C3'-''endo'' sugar conformation unlike the C2'-''endo'' conformation of the [[deoxyribose]] sugar in DNA. This forces an RNA double helix to change from a [[B-DNA]] structure to one more closely resembling [[A-DNA]].

RNA also uses a different set of bases than DNA—[[adenine]], [[guanine]], [[cytosine]] and [[uracil]], instead of adenine, guanine, cytosine and [[thymine]]. Chemically, uracil is similar to thymine, differing only by a [[methyl group]], and its production requires less energy.<ref>{{cite web |title=Uracil |url=http://www.humpath.com/spip.php?article7304 |access-date=2020-07-24 |url-status=live |archive-url=https://web.archive.org/web/20150908055138/http://www.humpath.com/spip.php?article7304 |archive-date=2015-09-08}}</ref> In terms of base pairing, this has no effect. Adenine readily binds uracil or thymine. Uracil is, however, one product of [[Deamination#Cytosine|damage to cytosine]] that makes RNA particularly susceptible to mutations that can replace a '''GC''' base pair with a '''GU''' ([[wobble base pair|wobble]]) or '''AU''' [[base pair]].

RNA is thought to have preceded DNA, because of their ordering in the biosynthetic pathways.<ref name="Robertson2012" /> The deoxyribonucleotides used to make DNA are made from ribonucleotides, the building blocks of RNA, by removing the 2'-hydroxyl group. As a consequence, a cell must have the ability to make RNA before it can make DNA.

==== Limitations of information storage in RNA ====
The chemical properties of RNA make large RNA [[molecule]]s inherently fragile, and they can easily be broken down into their constituent nucleotides through [[hydrolysis]].<ref>{{cite journal | vauthors = Lindahl T | title = Instability and decay of the primary structure of DNA | journal = Nature | volume = 362 | issue = 6422 | pages = 709–715 | date = April 1993 | pmid = 8469282 | doi = 10.1038/362709a0 | s2cid = 4283694 | bibcode = 1993Natur.362..709L }}</ref><ref>{{cite journal | vauthors = Pääbo S | title = Ancient DNA | journal = Scientific American | volume = 269 | issue = 5 | pages = 86–92 | date = November 1993 | pmid = 8235556 | doi = 10.1038/scientificamerican1193-86 | s2cid = 5288515 | bibcode = 1993SciAm.269e..86P }}</ref> These limitations do not make use of RNA as an [[information storage]] system impossible, simply energy intensive (to repair or replace damaged RNA molecules) and prone to mutation. While this makes it unsuitable for current 'DNA optimised' life, it may have been acceptable for more primitive life.

=== RNA as a regulator ===
{{Main|Riboswitch}}
Riboswitches have been found to act as regulators of gene expression, particularly in bacteria, but also in plants and [[archaea]]. Riboswitches alter their [[secondary structure]] in response to the binding of a [[metabolite]]. Riboswitch classes have highly conserved [[aptamer]] domains, even among diverse organisms. When a target metabolite is bound to this aptamer, conformational changes occur, modulating the expression of genes carried by mRNA. These changes occur in an expression platform, located downstream from the aptamer.<ref>{{Cite journal |last1=Winkler |first1=Wade C. |last2=Breaker |first2=Ronald R. |date=2005-10-01 |title=Regulation of Bacterial Gene Expression by Riboswitches |url=http://dx.doi.org/10.1146/annurev.micro.59.030804.121336 |journal=Annual Review of Microbiology |volume=59 |issue=1 |pages=487–517 |doi=10.1146/annurev.micro.59.030804.121336 |pmid=16153177 |issn=0066-4227}}</ref> This change in structure can result in the formation or disruption of a [[Terminator (genetics)|terminator]], truncating or permitting transcription respectively.<ref>{{cite journal | vauthors = Nudler E, Mironov AS | title = The riboswitch control of bacterial metabolism | journal = Trends in Biochemical Sciences | volume = 29 | issue = 1 | pages = 11–17 | date = January 2004 | pmid = 14729327 | doi = 10.1016/j.tibs.2003.11.004 }}</ref> Alternatively, riboswitches may bind or occlude the [[Shine–Dalgarno sequence]], affecting translation.<ref>{{cite journal | vauthors = Tucker BJ, Breaker RR | title = Riboswitches as versatile gene control elements | journal = Current Opinion in Structural Biology | volume = 15 | issue = 3 | pages = 342–348 | date = June 2005 | pmid = 15919195 | doi = 10.1016/j.sbi.2005.05.003 }}</ref> It has been suggested that these originated in an RNA-based world.<ref name="pmid18778966">{{cite journal | vauthors = Bocobza SE, Aharoni A | title = Switching the light on plant riboswitches | journal = Trends in Plant Science | volume = 13 | issue = 10 | pages = 526–533 | date = October 2008 | pmid = 18778966 | doi = 10.1016/j.tplants.2008.07.004 | bibcode = 2008TPS....13..526B }}</ref> In addition, [[RNA thermometer]]s regulate gene expression in response to temperature changes.<ref name="Nar06">{{cite journal | vauthors = Narberhaus F, Waldminghaus T, Chowdhury S | title = RNA thermometers | journal = FEMS Microbiology Reviews | volume = 30 | issue = 1 | pages = 3–16 | date = January 2006 | pmid = 16438677 | doi = 10.1111/j.1574-6976.2005.004.x | doi-access = free }}</ref>