Biomedical Engineering Reference
In-Depth Information
base. pairs). and. lack. any. analogous. packaging. within. the. cell. like. chromatin.. The. key.
chemical.difference.between.DNA.and.RNA.is.the.presence.of.a.hydroxyl.group.in.place.
of.hydrogen.in.the.2′.carbon.of.the.ribose.sugar..As.a.result,.double-stranded.RNA.will.
typically. form. a. more. compact. A-form. helix,. as. opposed. to. the. B-form. helix. of. DNA..
Though.this.2′.OH.group.is.susceptible.to.hydrolysis.and.enzymatic.attack,.unlike.DNA,.
it.plays.an.important.role.both.in.the.increased.thermodynamic.stability.of.RNA.and.in.
the.ability.of.RNA.to.bind.to.proteins,.forming.functional.complexes.(Searle.and.Williams.
1993;. Lesnik. and. Freier. 1995;. Sugimoto. et. al.. 1995).. However,. RNA. is. primarily. single.
stranded. within. the. cell. and. is. a. more. lexible. polymer. than. DNA,. allowing. for. a. far.
greater.number.of.possible.structural.variations.within.the.strand..The.local.conditions.
in.which.RNA.is.present.plays.a.major.role.in.its.global.folding,.be.it.inside.a.cell.with.the.
inluence.of.cellular.compartments.or.other.cellular.components.or.
in vitro
.in.a.buffer.with.
differing.salt.conditions.
5.2 Structural Order of RNA
RNA. structural. hierarchy. starts. with. the. basic. nucleotide. sequence. called. the. primary.
structure.(Figure.5.1a).with.the.major.difference.from.DNA.being.the.replacement.of.thy-
mine.with.uracil..The.secondary. structure.usually.involves.the.complementary.binding.
of.base.pairs.in.a.two-dimensional.form..RNA.polymers.can.form.internal.bonds.within.
the.sequence.of.the.RNA,.forming.secondary.structures.such.as.stems,.bulges,.loops,.and.
hairpins.(Figure.5.1b)..Tertiary.structure.is.not.merely.a.three-dimensional.representation.
of. RNA. but. also. includes. three-dimensional. interactions.. One. common. example. is. the.
pseudoknot,.wherein.a.loop.region.forms.base.pairs.with.a.single-stranded.portion.of.the.
same.molecule..Others.include.intramolecular.kissing.loops,.where.the.interactions.occur.
between.two.loop.regions.(Figure.5.1c).or.more.complex.structures.such.as.triplexes.and.
junctions..In.addition.to.these.interactions,.there.are.also.examples.showing.multiple.non-
interconvertible. structures. arising. out. of. a. single. primary. sequence. (Huang. et. al.. 2009),.
which.could.be.a.result.of.complex.tertiary.structures,.unusual.base.pairing,.or.a.combina-
tion.of.both..An.important.thing.to.remember.about.representations.of.RNA.structures.is.
that.they.are.almost.always.illustrated.as.two-dimensional.representations.for.the.sake.of.
simplicity..However,.these.interactions.are.predominantly.three-dimensional.and.should.
be.thought.of.as.possessing.multiple.twists.and.curves.in.and.out.of.the.plane.of.the.paper..
The.complexity.of.these.structures.allows.RNA.to.be.viewed.as.a.structural.analog.closer.
to.the.complicated.folds.and.structures.of.protein,.rather.than.the.comparatively.simple.
structure.of.DNA.
The. ability. to. form. secondary. and. tertiary. structures. is. highly. dependent. on.
the. unique. ability. of. RNA. molecules. to. form. a. larger. variety. of. stable. base. pairings.
than. are. present. in. DNA.. In. addition. to. the. usual. Watson-Crick. pairings,. RNA. also.
demonstrates.non-Watson-Crick.pairings.in.the.form.of.substantial.amounts.of.wobble.
base. pairing,. such. as. guanine-uracil. and. other. noncanonical. pairings. (Figure. 5.1b;.
Varani. and. McClain. 2000).. Rare. bonding. can. also. result. from. nonhydrogen. bonding-
related. stacking. of. sugars. with. base. pairs. (Searle. and. Williams. 1993;. Sugimoto. et. al..
1995;. Westhof. and. Fritsch. 2000).. These. pairings. are. not. as. energetically. stable. as. the.
canonical. base. pairings. but. contribute. to. and. enable. the. tertiary. motifs. necessary. for.
the. formation. of. more. complex. RNA. structures.. One. exception. is. the. high. thermal.
