Detection of internal repeats: How common are they?

Current Opinion in Structural Biology

Volumn 8, Issue 3, 1998, Pages 338-345

  Heringa, Jaap ^a  

^a NATIONAL INSTITUTE FOR MEDICAL RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

GENE DUPLICATION; GENETIC DISORDER; GENOME; NUCLEOTIDE REPEAT; PRIORITY JOURNAL; PROTEIN DEFECT; PROTEIN DOMAIN; PROTEIN STRUCTURE; REVIEW; SEQUENCE ANALYSIS; TANDEM REPEAT;

EID: 0032104544     PISSN: 0959440X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-440X(98)80068-7     Document Type: Article

References (66)

1. Cox R, Mirkin SM. Characteristic enrichment of DNA repeats in different genomes. of outstanding interest Proc Natl Acad Sci USA. 94:1997;5237-5242 This paper describes a comparison of the abundancies of inverted, direct tandem and homopurine - homopyrimidine mirror repeats in various prokaryotes, eukaryotes and an archaebacterium. Eukaryotes show an over-representation of all three repeat types, whereas the other two genome types only display enhanced inverted repeat frequencies. When normalised to expected frequencies, the over-represented eukaryotic repeat frequencies were shown to be an almost perfect exponential function of their lengths. There seems to be a pronounced evolutionary bias towards DNA that contains long repeats.
2. Ohno S. Evolution by Gene Duplication. 1970;George Allen and Unwin, London.
3. Wolfe KH, Shields DC. Molecular evidence for an ancient duplication of the entire yeast genome. Nature. 387:1997;708-713.
4. Kondo H, Ino M, Suzuki A, Ishizaki H, Iwami M. Multiple gene copies for bombyxin, an insulin-related peptide of the silkmoth Bombyx mori: structural signs for gene rearrangement and duplication responsible for generation of multiple molecular forms of bombyxin. J Mol Biol. 259:1996;926-937.
5. Jorde LB, Rogers AR, Bamshad M, Watkins WS, Krakowiak P, Sung S, Kere J, Harpending HC. Microsatellite diversity and the demographic history of modern humans. of special interest Proc Natl Acad Sci USA. 94:1997;3100-3103 The authors analysed 60 nuclear microsatellite systems (i.e. simple sequence repeats of two or three nucleotides) from various subpopulations of African, Asian and European origin. The study confirmed the "out of Africa" hypothesis, as African populations have a 20% greater microsatellite divergence those Asian and European populations, and thus should be older. The authors performed principal coordinate analyses of the microsatellite variability and found that the first two principal coordinate analyses clearly segregated the three groups, with the subpopulations for each main group forming close clusters. The greater diversity of African populations was clearest at loci with a smaller overall variance suggesting that evolutionary memory becomes blurred at fast mutating sites.
6. Virtaneva K, D'Amato E, Miao J, Koskiniemi N, Norio R, Avanzini G, Franceschetti S, Michelucci R, Tassinari CA, Omer S, et al. Unstable minisatellite expansion causing recessively inherited myoclonus epilepsy, EPM1. Nat Genet. 15:1997;393-396.
7. Sinden RR. DNA Structure and Function. 1994;Academic Press, San Diego.
8. Wells RD, Sinden RR. Defined ordered sequence DNA, DNA structure, and DNA-directed mutation. Davies KD, Warren ST. Genome Analysis. 7:1993;107-138 Cold Spring Harbor Laboratory Press, Plainview, New York.
9. Cosner ME, Jansen RK, Palmer JD, Downie SR. The highly rearranged chloroplast genome of Trachelium caeruleum (Campanulaceae): multiple inversions, inverted repeat expansion and contraction, transposition, insertions/deletions, and several repeat families. Curr Genet. 31:1997;419-429.
10. Kawata M, Harada T, Shimamoto Y, Oono K, Takaiwa F. Short inverted repeats function as hotspots of intermolecular recombination giving rise to oligomers of deleted plastid DNAs (ptDNAs). of special interest Curr Genet. 31:1997;179-184 Rice plastid DNA junction sites were analysed and it was found that 7-14 base pair inverted repeats occurred at either flank for all the sites. Plastid circular DNAs are known to be susceptible to recombination. Recombination that is mediated by these short inverted repeats can explain the occurrence of linear fused plastid DNA with large-scale deletions and the fusion of the remaining DNA sequences in an inverted orientation.
11. n repetitive tracts affect several stages of Rec-A-promoted recombination. of special interest J Mol Biol. 273:1997;105-113 GT repeats were investigated for a possible relationship between expansion number and binding to the RecA protein, which mediates homologous recombination. RecA binding turned out to have a strongly correlated affinity with the GT expansion number. Tight RecA binding results in the inhibition of DNA D-loop (exchange loop) and heteroduplex formation, and therefore blocks DNA strand exchange. Regions adjacent to such sites would have an increased preference for crossing-over events and illegitimate recombination.
12. Samadashwily GM, Raca G, Mirkin SM. Trinucleotide repeats affect DNA replication in vivo. of special interest Cell. 90:1997;549-558 The progression of replication forks during DNA replication was analysed in vivo for DNA from bacterial plasmids in which CTG (CAG) and CGG (CCG) trinucleotide repeats of various lengths had been incorporated. A negative correlation between repeat length and replication was found. Replication was also found to depend upon the directionality of the repeat and decreased over CAG, CTG, CCG and CGG repeats of identical length.
13. Hedjran F, Yeakley JM, Huh GS, Hynes RO, Rosenfeld MG. Control of alternative pre-mRNA splicing by distributed pentameric repeats. of outstanding interest Proc Natl Acad Sci USA. 94:1997;12343-12347 It is known that TGCATG hexamer repeats regulate the tissue-specific splicing of the fibronectin gene, thereby affecting the fibronectin type III copy number in rats (Figure 2). The pentamer repeat GCATG is investigated in this paper because it occurs nine times in the rat calcitonin/CGRP gene, with five of these occurrences located within the alternatively spliced portion of the gene. By removing various combinations of these five repeats, it was found that two or more repeats are needed for calcitonin-specific splicing, and that the presence of an intronic repeat as well as an exonic repeat is required. Strikingly, higher repeat numbers inhibited splicing. The opposite effect occurs in fibronectin, where multiple repeats enhance alternative splicing. This is possibly caused by differences both in the location of the native repeats and in the arrangement of the alternative exons within the fibronectin and the calcitonin/CGRP genes.
14. Mushegian AR, Bassett DE Jr, Bogusk MS, Bork P. Positionally cloned human disease genes: patterns of evolutionary conservation and functional motifs. of special interest Proc Natl Acad Sci USA. 94:1997;5831-5836 The authors used sensitive computer techniques, including the new Psiblast program, to analyse translated protein sequences from more than 70 human disease genes. Some new putative modules that were found include an ATP-binding domain in a colon cancer gene and a nuclease domain in a Werner syndrome protein.
15. Mizuki N, Ota M, Kimura M, Ohno S, Ando H, Katsuyame Y, Yamazaki M, Watanabe K, Goto K, Nakamura S, et al. Triplet repeat polymorphism in the transmembrane region of the MICA gene: a strong association of six GCT repetitions with Behçet disease. Proc Natl Acad Sci USA. 94:1997;1298-1303.
16. 1A-voltage-dependent calcium channel. Nat Genet. 15:1997;62-69.
17. Andrade MA, Bork P. HEAT repeats in the Huntington disease protein. Nat Genet. 11:1995;115-116.
18. Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, Bates GP, Davies SW, Lerach H, Wanker EE. Hungtintin-encoded polyglutamine expansions for amyloid-like protein aggregates in vitro and in vivo. of special interest Cell. 90:1997;549-558 Using electron microscopy, amyloid-like fibrils were observed after controllable proteolytic cleavage of a complex of glutathione S-transferase fused with huntingtin (GST-HD). Huntingtin's is located on Huntington's disease exon 1 and was expressed in E. coli. The mechanism proposed to explain the aggregation is that the very stable β-hairpin structures of pathologically long polyglutamine stretches in huntingtin are tightly bound to the GST-tag in the fused protein. After the GST parts are cleaved, the β hairpins become exposed, ready to form β sheets with other such loose β hairpins, thus assembling huntingtin aggregates. The observed regularly structured aggregates imply a nucleation-dependent polymerisation process for their formation.
19. n was found on the human chromosome 16 distamycin A fragile site FRA16B. Using positional cloning and polymerase chain reaction techniques, the site of these repeats was shown to be the only unstable fragment of the chromosome. On the same chromosome, 32 and 37 base-pair repeat motifs were also found but were ruled out as candidates for FRA16B. Further control experiments showed that the repeat region does not comprise pseudo-telomere repeats. The repeats were not perfect, as their lengths varied from 26 to 33 base pairs, with deletions occurring not only at the 5′ end but also at two internal sites within the motifs. Copy numbers varied from seven (in normal alleles) to 12. The structure of the FRA16B site can not be the normal B-DNA form when bound to the antiviral drug distamycin A, as this agent is known to fit only into narrow groove B′-DNA.
20. Berg ES, Olaisen B. Characterization of the COL2A1 VNTR polymorphism. Genomics. 16:1993;350-354.
21. Richards RI, Sutherland GR. Dynamic mutation: possible mechanisms and significance in human disease. Trends Biochem Sci. 22:1997;432-436.
22. Konig P, Giraldo R, Chapman L, Rhodes D. The crystal structure of the DNA-binding domain of yeast RAP1 in complex with telomeric DNA. Cell. 85:1996;125-136.
23. Chong L, van Steensel B, Broccoli D, Erdjument-Bromage H, Hanish J, Tempest P, de Lange T. A human telomeric protein. Science. 270:1995;1663-1667.
24. Konig P, Rhodes D. Recognition of telomeric DNA. Trends Biochem Sci. 22:1997;43-47.
25. Shore D. Telomerase and telomere-binding proteins: controlling the endgame. Trends Biochem Sci. 22:1997;233-235.
26. Wotton D, Shore D. A novel rap1p-interacting factor, rif2p, cooperates with rif1p to regulate telomere length in Sacharomyces cerevisiae. Genes Dev. 11:1997;748-760.
27. Nakayama J, Saito M, Nakamura H, Matsuura A, Ishikawa A. TLP1: a gene encoding a protein component of mammalian telomerase is a novel member of WD repeats family. of outstanding interest Cell. 88:1997;875-884 The telomerase protein component 1 (TLP1) gene encodes a 2629 amino acid sequence that contains four 30-residue repeats constituting the N-terminal 120 amino acids. The C-terminal part of the protein is composed of 16 WD-40 repeats, 15 of which are in tandem. The C-terminal repeat follows an intervening stretch that is tryptophan rich and therefore might also represent degenerate WD-40 repeats. If the function of the WD-40 repeats here is identical to that for WD-40 repeats in G proteins, then they would not be involved in telomeric DNA binding but rather in mediating the interaction of telomerase with several telomerase-binding proteins.
28. Tulko JS, Korotkov EV, Phoenix DA. MIRs are present in coding regions of human genes. of special interest DNA Seq. 8:1998;31-38 Using the repeats detection method based upon enlarged similarity (Korotkov et al. [29]) and a weighting function that emphasizes more conserved regions over variable ones, 12 new cases of mammalian interspersed repeats (MIRs) were detected in coding regions of proteins with a wide functional variety. For this detection, 49 previously known MIRs were used. MIRs are ancient repeat sets showing relatively few and interspersed conserved positions, rendering their detection difficult.
29. Korotkov EV, Korotkova MA, Tulko JS. Latent sequence periodicity of some oncogenes and DNA-binding protein genes. of special interest CABIOS. 13:1997;37-44 This paper describes a fast method for detecting tandem repeats in nucleotide sequences. All repeat lengths from two to 150 were tested and a 4 × N matrix (4 nucleotide symbols and N is the repeat length) containing mutual information was built, similar to a profile containing the nucleotide probabilities. Many mRNA sequences are shown to be repetitive. Two specific findings are a 45-base repeat in the human retinoblastoma susceptibility gene and a 84-base repeat in the human A-raf-1 oncogene.
30. Smit AFA, Riggs AD. MIRs are classic tRNA-derived SINEs that amplified before the mammalian radiation. Nucleic Acids Res. 23:1995;98-102.
31. Carlotti A, Thyagarajan S, Schroeppl K, Kvaal C, Villard J, Soll DR. A novel repeat sequence (CKRS-1) containing a tandemly repeated sub-element (kre) accounts for differences between Candida krusei strains fingerprinted with the probe CkF1,2. of special interest Curr Genet. 31:1997;255-263 This paper describes the discovery of a repeat number polymorphism for a 165 base pair tandemly repeated kre subelement in the CKRS-1 sequence, which is located on an intergenic region of ribosomal RNA cistrons in Candida krusei. CKRS-1 sequences containing five, six, seven and eight kre repeats were found. The kre repeats are all similar to identical and the lowest pairwise sequence identity between them was 66%. Inverted repeats and the pronounced variability found outside the kre repeat regions and terminal in CKRS-1 sequences suggest that the observed kre polymorphism resulted from evolutionary events within the various kre repeat regions.
32. Heringa J, Taylor WR. Three-dimensional domain duplication, swapping and stealing. of special interest Curr Opin Struct Biol. 7:1997;416-421 This review describes evolutionary pathways to multidomain protein organisations and includes a few intricate examples, such as MHC class I and II divergence, HIV reverse transcriptase domain rearrangements and the relationship between the zinc finger and RING motifs. An overview is given of the association between sequential repeats and protein structure.
33. Bork P, Schultz J, Ponting CP. Cytoplasmic signalling domains: the next generation. Trends Biochem Sci. 22:1997;296-298.
34. Henikoff S, Greene EA, Pietrokovski S, Bork P, Attwood TK, Hood L. Gene families: the taxonomy of protein paralogs and chimera. Science. 278:1997;609-614.
35. Riley M, Labedan B. Protein evolution viewed through Escherichia coli protein sequences: introducing the notion of a structural segment of homology, the module. J Mol Biol. 268:1997;857-868.
36. Frank S, Kostner GM. The role of apo-(a) kringle-ivs in the assembly of lipoprotein-(a). Protein Eng. 10:1997;291-298.
37. Lupas A, Baumeister W, Hofmann K. A repetitive sequence in subunits of the 26s proteasome and 20s cyclosome (anaphase-promoting complex). of special interest Trends Biochem Sci. 22:1997;195-196 In this paper, it is suggested that repeats in the 26S proteasome and the 20S cyclosome would associate in a similar way to the repeated α helices in leucine-rich repeat (LRR) proteins. The smaller number of repeats in the 26S and 20S proteins when compared to LRR proteins would give rise to an incomplete horseshoe structure, containing an exposed phase of mainly alanine and glycine residues that would unspecifically bind to damaged proteins.
38. Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB. Crystal structure of a G protein βγ dimer at 2.1-angstrom resolution. Nature. 379:1996;369-374.
39. Springer TA. Folding of the N-terminal, ligand-binding region of integrin α-subunits into a β-propeller domain. of special interest Proc Natl Acad Sci USA. 94:1997;65-72 This paper describes the steps taken to predict the very likely fold of the N-terminal, ligand-binding domain of the integrin α subunit. The region is composed of seven so-called FG-GAP repeats, each of about 60 amino acids. A β-propeller structure with extensive inter-repeat structural contacts was proposed rather than seven independently folded tandem domains given that: first, the number of possible disulfide bonds within each repeat is smaller than that normally expected for small independent domains, such that interdomain bridges are suspected; second, each repeat contains two long completely hydrophic stretches (consenus sequences are VVVGAP and VYLF) that would not fit within the core of a small domain; and third, the number of repeats seen in integrins is always seven and not variable as in cases of beads on a string tandem repeats. As the secondary structure of each of the seven repeats was predicted to be composed of β strands the most likely candidate over the known folds was a seven-bladed β-propellor fold. A three-dimensional model was constructed by homology modeling using two putative homologous proteins with known structure, galactose oxidase (GO) and the G protein β subunit (G beta).
40. Heringa J, Frishman D, Argos P. Computational methods relating protein sequence and structure. of special interest Allen G. Proteins: a Comprehensive Treatise. Volume 1: Principles of Protein Structure. 1997;171-277 JAI press, New York, This extensive review covers the major aspects of computational methods relating protein sequence and structure. It is intended for the novice reader and topics include: sequence comparison; motif searching; phylogenetic methods; structure prediction; protein folding; and inverse folding methods.
41. Heringa J, Langosch D. Interaction of transmembrane helices by a knobs-into-holes packing characteristic of soluble coiled coils. of special interest Proteins. 31:1998;150-160 Interresidue contacts in transmembrane helical packing were analysed for photosynthetic reaction centers, bacteriorhodopsin and cytochrome c. The vast majority of the residue - residue contacts conform to the knobs into holes type of packing found in leucine zippers of many soluble proteins. The packing of the transmembrane helical bundles is, however, less compact and less regular than that of soluble coiled-coils. Moreover, the amino acid composition of the heptad repeats is distinctly different, with the charged residues found in soluble helices substituted by apolar acids in the transmembrane zippers.
42. Peters J, Baumeister W, Lupas A. Hyperthermostable surface-layer protein tetrabrachion from the archaebacterium Staphylothermus marinus - evidence for the presence of a right-handed coiled-coil derived from the primary structure. J Mol Biol. 257:1996;1031-1041.
43. MacKenzie KR, Prestegard JH, Engelman DM. Gene duplications in the structural evolution of chymotrypsin. Science. 276:1997;131-133.
44. Muhle-Goll C, Nilges M, Pastore A. The leucine zippers of the HLH-LZ proteins MAX and C-MYC preferentially form heterodimers. Biochemistry. 34:1995;13554-13564.
45. Zhang B, Gallegos M, Puoti A, Durkin E, Fileds S, Kimble J, Wickens MP. A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line. of special interest Nature. 390:1997;477-484 Eight Puf repeats detected in C. elegans FBF were also found in Drosophila pumilio, a protein that mediates pattern formation. Puf repeats are also found in other proteins of this Puf family but only FBF and pumilio act as repressors, because the eight Puf repeats probably fold as a single protein domain that, in the case of C. elegans, binds the 3′ untranslated region of the mRNA molecule fem-3 responsible for the switch from spermatogenesis to oogenesis.
46. Hegyi H, Bork P. On the classification and evolution of protein modules. of special interest J Prot Chem. 16:1997;545-551 In this paper, the current classification of protein modules is reviewed. In eukaryotes, the number of modular proteins is dramatically correlated with the evolution from single to multicellular organisms. A novel sequence and module alerting system is introduced that is able to check new sequence data for the presence of known domains. Using this software, the authors found surprising similarities between the extracellular C1Q module and some bacterial protein sequences.
47. Tsang AP, Visvader JW, Turner CA, Fujiwara Y, Yu C, Weiss MJ, Crossley M, Orkin SH. FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryotic differentiation. Cell. 90:1997;109-119.
48. Tapia-Ramirez J, Eggen BJL, Peral-Rubio MJ, Toledo-Aral JJ, Mandel G. A single zinc finger motif in the silencing factor REST represses the neural-specific type II sodium channel promoter. Proc Natl Acad Sci USA. 94:1997;1177-1182.
49. 2+-release channels). Trends Biochem Sci. 22:1997;193-194.
50. Ponting CP. Tudor domains in proteins that interact with RNA. Trends Biochem Sci. 22:1997;51-52.
51. Bork P, Hofmann K, Bucher P, Neuwald AF, Altschul AF, Koonin WV. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins. of special interest FASEB J. 11:1997;68-76 The BRCT (breast cancer protein 1 C terminus) domain is conserved through a wide range of species and proteins. It is seen to occur in up to four tandem copies and is implicated in DNA-damage responsive cell-cycle checkpoints, although most direct evidence points at transcription regulation. No amino acid is completely conserved in the multiple alignment of BRCT sequences. A BRCT domain is also found directly preceding the DNA-binding domain in the telomere-binding protein RAP1.
52. Gerstein M. A structural census of genomes: comparing bacterial, eukaryotic, and archaeal genomes in terms of protein structure. of outstanding interest J Mol Biol. 274:1997;562-576 In this paper, the genomes of the bacterium Haemofilus influenza, the archaeon Methanococcus jannaschii and eukaryotic yeast are compared. Translated genome sequences were taken from the open reading frames of each of the three genomes. No state of the art procedures in terms of sensitivity were adopted for sequence comparison (FASTA) and secondary structure prediction (GOR) but the author argues that using other methods could create biases in the recognition of particular folds. Strikingly, H. influenza was found to have the highest fraction of proteins of the α class (e.g. α - α - α - patterns), M. jannaschii showed preponderant alternating α - β proteins, whereas the greatest portion in yeast was β-type proteins (e.g. β - β - β secondary structures). Nonetheless, yeast had the largest fraction of membrane proteins (with at least two consecutive transmembrane α helices). The Haemofilus and Methanococcus genomes are of a similar size (about 1700 proteins recognised in both), although the yeast genome is larger, with 6200 inferred sequences. Moreover, the average length of yeast proteins (470 residues) was much greater than those for proteins from the other two genomes (about 295 for both), indicating that the abundant gene duplications probably enhanced the number of gene fusion events.
53. Murzin AG, Brenner SE, Hubbard T, Chothia C. SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol biol. 247:1995;536-540.
54. Kachroo P, Ahuja M, Leong SA, Chattoo BB. Organisation and molecular analysis of repeated DNA sequences in the rice blast fungus Magnaporthe grisea. Curr Genet. 31:1997;361-369.
55. McLachlan AD. Gene duplications in the structural evolution of chymotrypsin. J Mol Biol. 128:1979;49-79.
56. Musacchio A, Gibson T, Rice P, Thompson J, Saraste M. The PH domain: a common piece in the structural patchwork of signaling proteins. Trends Biochem Sci. 18:1993;343-348.
57. Heringa J, Argos P. A method to recognize distant repeats in protein sequences. Proteins. 17:1993;391-411.
58. Heringa J. The evolution and recognition of protein sequence repeats. Comput Chem. 17:1994;233-243.
59. Lupas A, Van Dyke M, Stock J. Predicting coiled coils from protein sequences. Science. 252:1991;1162-1164.
60. Smith TF, Waterman MS. Identification of common molecular subsequences. J Mol Biol. 147:1981;195-197.
61. Boguski MS, Hardison RC, Schwartz S, Miller W. Analysis of conserved domains and sequence motifs in cellular regulatory proteins and locus-control regions using new software tools for multiple alignment and visualization. New Biol. 4:1992;247-260.
62. Index of Mathbio on World Wide Web URL: http://www.nimr.mrc.ac.uk/mathbio/ The REPRO method [57,58] detects repeats in a single protein sequence by exploiting best scoring local nonoverlapping alignments from which one or more disjunct repeat sets can be built through consistency checks of the repeat start sites. An iterative graph-based clustering algorithm is designed to enable consistency checks for the various included sequence stretches pertaining to a particular repeat type. Growth of a repeat ensemble in subsequent iterations can lead to the inclusion of fragments that were rejected before. The method only needs a single query sequence and does not require the number of amino acids suspected in a possible repeat as input. It produces multiple alignments of the repeat sets found together and also gives the initial top scoring alignments that they were derived from. Efforts are currently underway to implement a REPRO server environment at the mentioned website.
63. Lawrence CE, Altschul SF, Boguski MS, Liu JS, Neuwald F, Wootton JC. Detecting subtle sequence signals - a Gibbs sampling strategy for multiple alignment. Science. 262:1993;208-214.
64. Benson G. Sequence alignment with tandem duplication. of special interest J Comput Biol. 4:1997;351-367 This paper describes a new algorithm that incorporates the detection of tandem repeats in the alignment of a pair of sequences. The algorithm makes use of a clever alteration of the classic local alignment dynamic programming algorithm [60].
65. Zhang S, Rich A. Direct conversion of an oligopeptide from a β-sheet to and helix: a model for amyloid formation. of outstanding interest Proc Natl Acad Sci USA. 94:1997;23-28 This paper describes the folding of a set of self-complementary 16 amino acid oligopeptides. One of these peptides, DAR16-IV (ADADADADARARARAR), forms a stable and probably antiparallel β-sheet structure in water. On incubation and at temperatures higher than 70°C, it performs a structural transition from β sheet directly into an α helix without any observable random coil intermediate. The thus formed helices are very stable as it takes weeks at room temperature to partially return to the original β-sheet form. It will be interesting to see how important interhelix contacts are in this sudden refolding.
66. Uhlenbeck OC, Pardi A, Feigon J. RNA structure comes of age. Cell. 90:1997;833-840.