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Tetraloops are a type of four-base hairpin loop motifs in RNA secondary structure that cap many double helices. There are many variants of the tetraloop. The published ones include ANYA, CUYG, GNRA, UNAC and UNCG.
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.
- 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, 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° 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.
- In the UNCG is favorable thermodynamically and structurally due to hydrogen bonding. van der Waals interactions, 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. UUCG and GNRA tetraloops make up 70% of all tetraloops in 16S-RNA .
- Cate, J.H., Gooding, A.R., Podell, E., Zhou, K., Golden, B.L., Kundrot, C.E., Cech, T.R., Doudna, J.A. (1996). "Crystal structure of a group I ribozyme domain: principles of RNA packing". Science. 273 (5282): 1676–1685. doi:10.1126/science.273.5282.1678. PMID 8781224.
- Woese, C.R., Winkers, S., Gutell, R.R. (1990). "Architecture of ribosomal RNA: Constraints on the sequence of "tetra-loops"". Proc. Natl. Acad. Sci. USA. 87 (21): 8467–71. doi:10.1073/pnas.87.21.8467. PMC . PMID 2236056.
- Zirbel, CL; Sponer, JE; Sponer, J; Stombaugh, J; Leontis, NB (Aug 2009). "Classification and energetics of the base-phosphate interactions in RNA". Nucleic Acids Research. 37 (15): 4898–918. doi:10.1093/nar/gkp468. PMC . PMID 19528080.
- Klosterman, PS; Hendrix, DK; Tamura, M; Holbrook, SR; Brenner, SE (2004). "Three-dimensional motifs from the SCOR, structural classification of RNA database: extruded strands, base triples, tetraloops and U-turns". Nucleic Acids Research. 32 (8): 2342–52. doi:10.1093/nar/gkh537. PMC . PMID 15121895.
- Jucker, FM; Pardi, A (Nov 7, 1995). "Solution structure of the CUUG hairpin loop: a novel RNA tetraloop motif". Biochemistry. 34 (44): 14416–27. doi:10.1021/bi00044a019. PMID 7578046.
- Jaeger, L; Michel, F; Westhof, E (Mar 11, 1994). "Involvement of a GNRA tetraloop in long-range RNA tertiary interactions". Journal of Molecular Biology. 236 (5): 1271–6. doi:10.1016/0022-2836(94)90055-8. PMID 7510342.
- Zhao, Q; Huang, HC; Nagaswamy, U; Xia, Y; Gao, X; Fox, GE (Aug 2012). "UNAC tetraloops: to what extent do they mimic GNRA tetraloops?". Biopolymers. 97 (8): 617–28. doi:10.1002/bip.22049. PMID 22605553.
- Molinaro, M; Tinoco I, Jr (Aug 11, 1995). "Use of ultra stable UNCG tetraloop hairpins to fold RNA structures: thermodynamic and spectroscopic applications". Nucleic Acids Research. 23 (15): 3056–63. doi:10.1093/nar/23.15.3056. PMC . PMID 7544890.
- Baumruk, Vladimir; Gouyette, Catherine; Huynh-Dinh, Tam; Sun, Jian-Sheng; Ghomi, Mahmoud (2001-10-01). "Comparison between CUUG and UUCG tetraloops: thermodynamic stability and structural features analyzed by UV absorption and vibrational spectroscopy". Nucleic Acids Research. 29 (19): 4089–4096. doi:10.1093/nar/29.19.4089. ISSN 0305-1048. PMC . PMID 11574692.
- Zhao, Q., Huang, H-C., Nagaswamy, U., Xia, Y., Gao, X., Fox, G.E. (2012). "UNAC tetraloops: To what extent do they mimic GNRA tetraloops?". Biopolymers. 97 (8): 617–628. doi:10.1002/bip.22049. PMID 22605553.
- Heus, Hans A.; Pardi, Arthur (1991-01-01). "Structural Features that Give Rise to the Unusual Stability of RNA Hairpins Containing GNRA Loops". Science. 253 (5016): 191–194. doi:10.1126/science.1712983. JSTOR 2878700.
- Antao, V. P.; Lai, S. Y.; Tinoco, I. (1991-11-11). "A thermodynamic study of unusually stable RNA and DNA hairpins". Nucleic Acids Research. 19 (21): 5901–5905. doi:10.1093/nar/19.21.5901. ISSN 0305-1048. PMC . PMID 1719483.
- Woese, C. R.; Winker, S.; Gutell, R. R. (1990-11-01). "Architecture of ribosomal RNA: constraints on the sequence of "tetra-loops"". Proceedings of the National Academy of Sciences of the United States of America. 87 (21): 8467–8471. doi:10.1073/pnas.87.21.8467. ISSN 0027-8424. PMC . PMID 2236056.
- Hall, Kathleen B. (October 15, 2013). "RNA does the folding dance of twist, turn, stack". Proceedings of the National Academy of Sciences of the United States of America. 110 (42): 16706–7. doi:10.1073/pnas.1316029110. JSTOR 23750643. PMC .
- Baumruk, V; Gouyette, C; Huynh-Dinh, T; Sun, JS; Ghomi, M (1 October 2001). "Comparison between CUUG and UUCG tetraloops: thermodynamic stability and structural features analyzed by UV absorption and vibrational spectroscopy". Nucleic Acids Research. 29 (19): 4089–96. doi:10.1093/nar/29.19.4089. PMC . PMID 11574692.
|This molecular biology article is a stub. You can help Wikipedia by expanding it.|
You can either download the motif alignment or view it directly in your browser window. More...
You can download (or view in your browser) a text representation of a Rfam alignment in various formats:
- Gapped FASTA
- Ungapped FASTA
You can view or download motif alignments in several formats. Check either the "download" button, to save the formatted alignment, or "view", to see it in your browser window, and click "Generate".
There are 15 PDB entires which have been used to build the motif model.
The table of results below may be sorted by clicking on the column titles, or restored to the original order .
|Original order||PDB ID||PDB chain ID||PDB Residues|
|2||1D0T||A||1 - 21|
|2||1RHT||A||1 - 24|
|2||17RA||A||1 - 20|
|2||2C51||R||1 - 19|
There is 1 Rfam family which matches this motif.
This section shows the families which have been annotated with this motif. Users should be aware that the motifs are structural constructs and do not necessarily conform to taxonomic boundaries in the way that Rfam families do. More...
To annotate the family with a motif model, the seed sequence was first filtered using a 0.9 fraction identity cut-off. The filtered seed was then scanned using Infernal cmscan (v1.1) with a concatenated CM file containing each of the motifs. Significance of hits between a seed sequence and the CM was based on a gathering threshold that was individually set for each motif. Only motifs where more than two and at least 10% of seed sequences scored higher than the gathering threshold were included for the next stage of processing. These subsets of motifs were then rescanned against the entire (non-filtered) seed to generate matches.
Number of Hits: the number of sequences in the family seed that score above the gathering threshold from motif.
Fraction of Hits: the fraction of sequences in the family seed that score above the gathering threshold from motif.
Sum of Bits: the sum of the bit scores of matches between the motif and the family seed sequence.
Image: plot illustrating where on the consensus secondary structure matches occur between seed sequences and the motif model.
|Original order||Family Accession||Family Description||Number of Hits||Fraction of Hits||Sum of Bits||Image|
|3||RF02359||Bacteriophage MS2 operator hairpin||5||1.000||141.5|
This section shows the database cross-references that we have for this Rfam motif.
Convery MA, Rowsell S, Stonehouse NJ, Ellington AD, Hirao I, Murray JB, Peabody DS, Phillips SE, Stockley PG Nat Struct Biol. 1998;5:133–139. Crystal structure of an RNA aptamer-protein complex at 2.8 A resolution. PUBMED:9461079
Rowsell S, Stonehouse NJ, Convery MA, Adams CJ, Ellington AD, Hirao I, Peabody DS, Stockley PG, Phillips SE. Nat Struct Biol. 1998;5(11):970-975. Crystal structures of a series of RNA aptamers complexed to the same protein target. PUBMED:9808042
Klosterman PS, Hendrix DK, Tamura M, Holbrook SR, Brenner SE Nucleic Acids Res. 2004;32:2342-52. Three-dimensional motifs from the SCOR, structural classification of RNA database: extruded strands, base triples, tetraloops and U-turns. PUBMED:15121895
External database links
Curation and motif details
This section shows the detailed information about the Rfam motif. We're happy to receive updated or improved alignments for new or existing families. Submit your new alignment and we'll take a look.
|Seed source||Published; PMID:19528080|
cmbuild -F CM SEED
cmcalibrate --mpi --seed 1 CM
|Covariance model||Download the Infernal CM for the motif here|