View source for Tetraloop

[[File:GNRA tetraloop.jpg|thumb|right|250 px|Structure of a GNRA tetraloop from a group I self-splicing [[intron]].<ref>{{cite journal | author=Cate, J.H., Gooding, A.R., Podell, E., Zhou, K., Golden, B.L., Kundrot, C.E., Cech, T.R., Doudna, J.A.| title=Crystal structure of a group I ribozyme domain: principles of RNA packing. | journal=Science| year=1996| volume=273| pages=1676–1685| pmid= 8781224 | doi=10.1126/science.273.5282.1678 | issue=5282 | bibcode=1996Sci...273.1678C | s2cid=38185676 }}</ref>]]
'''Tetraloops''' are a type of four-base [[hairpin loop]] [[structural motif|motif]]s in [[Nucleic acid secondary structure|RNA secondary structure]] that cap many [[double helices]].<ref name="Woese1990">{{cite journal | author=Woese, C.R., Winkers, S., Gutell, R.R.| title=Architecture of ribosomal RNA: Constraints on the sequence of "tetra-loops"| journal=Proc. Natl. Acad. Sci. USA| year=1990| volume=87| pages=8467–71| pmid=2236056| doi=10.1073/pnas.87.21.8467 | issue=21 | pmc=54977| bibcode=1990PNAS...87.8467W| doi-access=free}}</ref> There are many variants of the tetraloop. The published ones include ANYA,<ref>{{cite journal|last1=Zirbel|first1=CL|last2=Sponer|first2=JE|last3=Sponer|first3=J|last4=Stombaugh|first4=J|last5=Leontis|first5=NB|title=Classification and energetics of the base-phosphate interactions in RNA.|journal=Nucleic Acids Research|date=Aug 2009|volume=37|issue=15|pages=4898–918|pmid=19528080|doi=10.1093/nar/gkp468|pmc=2731888}}</ref><ref>{{cite journal|last1=Klosterman|first1=PS|last2=Hendrix|first2=DK|last3=Tamura|first3=M|last4=Holbrook|first4=SR|last5=Brenner|first5=SE|title=Three-dimensional motifs from the SCOR, structural classification of RNA database: extruded strands, base triples, tetraloops and U-turns.|journal=Nucleic Acids Research|date=2004|volume=32|issue=8|pages=2342–52|pmid=15121895|doi=10.1093/nar/gkh537|pmc=419439}}</ref>
CUYG,<ref>{{cite journal|last1=Jucker|first1=FM|last2=Pardi|first2=A|title=Solution structure of the CUUG hairpin loop: a novel RNA tetraloop motif.|journal=Biochemistry|date=Nov 7, 1995|volume=34|issue=44|pages=14416–27|pmid=7578046|doi=10.1021/bi00044a019}}</ref> 
GNRA,<ref>{{cite journal|last1=Jaeger|first1=L|last2=Michel|first2=F|last3=Westhof|first3=E|title=Involvement of a GNRA tetraloop in long-range RNA tertiary interactions.|journal=Journal of Molecular Biology|date=Mar 11, 1994|volume=236|issue=5|pages=1271–6|pmid=7510342|doi=10.1016/0022-2836(94)90055-8}}</ref>
UNAC<ref name="Zhao2012">{{cite journal|last1=Zhao|first1=Q|last2=Huang|first2=HC|last3=Nagaswamy|first3=U|last4=Xia|first4=Y|last5=Gao|first5=X|last6=Fox|first6=GE|title=UNAC tetraloops: to what extent do they mimic GNRA tetraloops?|journal=Biopolymers|date=Aug 2012|volume=97|issue=8|pages=617–28|pmid=22605553|doi=10.1002/bip.22049}}</ref>
and UNCG.<ref>{{cite journal|last1=Molinaro|first1=M|last2=Tinoco I|first2=Jr|title=Use of ultra stable UNCG tetraloop hairpins to fold RNA structures: thermodynamic and spectroscopic applications.|journal=Nucleic Acids Research|date=Aug 11, 1995|volume=23|issue=15|pages=3056–63|pmid=7544890|doi=10.1093/nar/23.15.3056|pmc=307149}}</ref>

Three types of tetraloops are common in [[ribosomal RNA]]: GNRA, UNCG and CUUG, in which the N could be either [[uracil]], [[adenine]], [[cytosine]], or [[guanine]], and the R is either guanine or adenine. These three sequences form stable and conserved tetraloops that play an important role in structural stability and biological function of 16S rRNA.<ref name="Baumruk2001">{{Cite journal|last1=Baumruk|first1=Vladimir|last2=Gouyette|first2=Catherine|last3=Huynh-Dinh|first3=Tam|last4=Sun|first4=Jian-Sheng|last5=Ghomi|first5=Mahmoud|date=2001-10-01|title=Comparison between CUUG and UUCG tetraloops: thermodynamic stability and structural features analyzed by UV absorption and vibrational spectroscopy|journal=Nucleic Acids Research|volume=29|issue=19|pages=4089–4096|issn=0305-1048|pmc=60239|pmid=11574692|doi=10.1093/nar/29.19.4089}}</ref>
* '''GNRA'''
** The GNRA tetraloop has a [[guanine]]-[[adenine]] base-pair where the guanine is 5' to the helix and the adenine is 3' to the helix. Tetraloops with the sequence UMAC have essentially the same backbone fold as the GNRA tetraloop,<ref name="Zhao2012"/> but may be less likely to form tetraloop-receptor interactions. They may therefore be a better choice for closing stems when designing artificial RNAs.
** The presence of the GNRA tetraloop  provides an exceptional stability to RNA structure. GNRA occurs 50% more than other tetranucleotides due to their ability to withstand temperatures 4&nbsp;°C higher than other RNA hairpins. This allows them to act as nucleation sites for proper folding of RNA. The rare hydrogen bonds between the first guanine and fourth adenine nucleotide, extensive stacking of nucleotide bases and hydrogen bonds between 2' OH of a ribose sugar and nitrogenous bases makes the tetraloop thermodynamically stable.<ref>{{Cite journal|last1=Heus|first1=Hans A.|last2=Pardi|first2=Arthur|date=1991-01-01|title=Structural Features that Give Rise to the Unusual Stability of RNA Hairpins Containing GNRA Loops|jstor=2878700|journal=Science|volume=253|issue=5016|pages=191–194|doi=10.1126/science.1712983|pmid=1712983|bibcode=1991Sci...253..191H}}</ref>
* '''UNCG'''
** In the UNCG  is favorable thermodynamically and structurally due to [[hydrogen bond]]ing, [[Van der Waals force|van der Waals]] interactions, [[Coulombic attraction|coulombic interactions]] and the interactions between the RNA and the solvent. The UNCG tetraloops are more stable than DNA loops with the same sequence. The UUCG tetraloop is the most stable tetraloop.<ref>{{Cite journal|last1=Antao|first1=V. P.|last2=Lai|first2=S. Y.|last3=Tinoco|first3=I.|date=1991-11-11|title=A thermodynamic study of unusually stable RNA and DNA hairpins|journal=Nucleic Acids Research|volume=19|issue=21|pages=5901–5905|issn=0305-1048|pmc=329045|pmid=1719483|doi=10.1093/nar/19.21.5901}}</ref>  UUCG and GNRA tetraloops make up 70% of all tetraloops in 16S-rRNA .<ref name="Woese1990"/>
* '''CUUG'''
** The CUUG tetraloop has the highest likelihood of conformational changes due to its structural flexibility. Out of the three tetraloops mentioned, this tetraloop is the most flexible since the second uracil is comparatively unrestricted.<ref>{{cite journal|date=October 15, 2013|title=RNA does the folding dance of twist, turn, stack|jstor=23750643|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=110|issue=42|pages=16706–7|last1=Hall|first1=Kathleen B.|doi=10.1073/pnas.1316029110|pmc=3801021|pmid=24072647|bibcode=2013PNAS..11016706H|doi-access=free}}</ref> It is also very thermodynamically stable.<ref name="Baumruk2001"/>
==See also==
*[[Nucleic acid tertiary structure|RNA tertiary structure]] (section [[RNA Tertiary Structure#Tetraloop-receptor interactions|Tetraloop-receptor interactions]])

==References==
<references/>

{{Biomolecular structure}}

[[Category:RNA]]


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