PubMed HealthSearch

PubMed · 7685689

RNA multi-structure landscapes. A study based on temperature dependent partition functions.

Abstract

Statistical properties of RNA folding landscapes obtained by the partition function algorithm (McCaskill 1990) are investigated in detail. The pair correlation of free energies as a function of the Hamming distance is used as a measure for the ruggedness of the landscape. The calculation of the partition function contains information about the entire ensemble of secondary structures as a function of temperature and opens the door to all quantities of thermodynamic interest, in contrast with the conventional minimal free energy approach. A metric distance of structure ensembles is introduced and pair correlations at the level of the structures themselves are computed. Just as with landscapes based on most stable secondary structure prediction, the landscapes defined on the full biophysical GCAU alphabet are much smoother than the landscapes restricted to pure GC sequences and the correlation lengths are almost constant fractions of the chain lengths. Correlation functions for multi-structure landscape exhibit an increased correlation length, especially near the melting temperature. However, the main effect on evolution is rather an effective increase in sampling for finite populations where each sequence explores multiple structures.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

S Bonhoeffer, J S McCaskill, P F Stadler, P Schuster. 1993. RNA multi-structure landscapes. A study based on temperature dependent partition functions.. https://doi.org/10.1007/bf00205808

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Recognition of DNA alterations by the mismatch repair system.

Misincorporation of non-complementary bases by DNA polymerases is a major source of the occurrence of promutagenic base-pairing errors during DNA replication or repair. Base-base mismatches or loops of extra bases can arise which, if left unrepaired, will generate point or frameshift mutations respectively. To counteract this mutagenic potential, organisms have developed a number of elaborate surveillance and repair strategies which co-operate to maintain the integrity of their genomes. An important replication-associated correction function is provided by the post-replicative mismatch repair system. This system is highly conserved among species and appears to be the major pathway for strand-specific elimination of base-base mispairs and short insertion/deletion loops (IDLs), not only during DNA replication, but also in intermediates of homologous recombination. The efficiency of repair of different base-pairing errors in the DNA varies, and appears to depend on multiple factors, such as the physical structure of the mismatch and sequence context effects. These structural aspects of mismatch repair are poorly understood. In contrast, remarkable progress in understanding the biochemical role of error-recognition proteins has been made in the recent past. In eukaryotes, two heterodimers consisting of MutS-homologous proteins have been shown to share the function of mismatch recognition in vivo and in vitro. A first MutS homologue, MSH2, is present in both heterodimers, and the specificity for mismatch recognition is dictated by its association with either of two other MutS homologues: MSH6 for recognition of base-base mismatches and small IDLs, or MSH3 for recognition of IDLs only. Mismatch repair deficiency in cells can arise through mutation, transcriptional silencing or as a result of imbalanced expression of these genes.

Base Composition

Fluorescence energy transfer as a probe for tetraplex formation: the i-motif.

The secondary structure of cytosine-rich oligodeoxynucleotides has been investigated with fluorescent probes. Intramolecular folding of an oligonucleotide into an i-DNA motif led to fluorescence excitation energy transfer between a donor (fluorescein) and an acceptor (tetramethylrhodamine) covalently attached to the 5' and 3' ends of the DNA, respectively, provided that a suitable linker was chosen. The conjugation of the dyes to the oligonucleotide had an influence on the thermodynamics of i-motif formation as well as on the kinetics of folding. Intramolecular folding was demonstrated from the concentration independence of FRET over a wide concentration range. Folding of the oligonucleotide was confirmed by UV absorption melting experiments. The folding of the i-motif could be followed at concentrations as low as 50 pM. Fluorescence energy transfer can thus be used to reveal the formation of multistranded DNA structures.

Base Composition

Variant effects of non-native kissing-loop hairpin palindromes on HIV replication and HIV RNA dimerization: role of stem-loop B in HIV replication and HIV RNA dimerization.

The genome of all retroviruses consists of two identical RNAs noncovalently linked near their 5' end. In vitro synthesized RNAs from human immunodeficiency virus type 1 (HIV-1) can form loose or tight dimers depending on whether their respective kissing-loop hairpins (nts 248-270 in HIV-1Lai) bond via their hexameric autocomplementary sequences (ACS), also called palindromes, or via the ACS and stem sequences [Laughrea, M., and Jetté, L. (1996) Biochemistry 35, 1589-1598]. To understand the role of the ACS in HIV-1 replication and in the formation and stability of HIV-1 RNA dimers, we replaced the central CGCG261(or tetramer) of the HIV-1Lai ACS by two other HIV-1 tetramers (UGCA/UGCG), four non-HIV-1 tetramers [GUAC, UUAA (respectively found in HIV-2Rod and SIVmnd), GGCC and AGCU (absent from HIV and SIV viruses)], or GGCG, a nonpalindromic tetramer. The infectivity of GGCC, GUAC, and UGCA viruses was unchanged or insignificantly decreased; the infectivity of AGCU and UGCG viruses was decreased by 80%; the infectivity of UUAA and GGCG viruses was decreased by 92-98%. Thus, the four non-HIV-1 palindromes yielded phenotypes ranging from wild-type to as defective as a virus bearing a nonpalindrome. Studies of in vitro synthesized HIV-1 RNAs were generally consistent with in vivo results, specifically: (i) loose dimerization of GGCC and GUAC RNAs, but not of UUAA and AGCU RNAs, was influenced by the 3' DLS (a sequence located downstream of the 5' splice junction) in a way expected for a wild-type ACS; (ii) the 3' DLS strongly reduced tight dimerization of UUAA and AGCU RNAs, but not of GGCC and GUAC RNAs. We conclude that HIV-1 is sensitive to the ACS sequence without discriminating against all nonnative ACS: GGCC/GUAC, but not AGCU/UUAA, are good substitutes for the prevalent CGCG/UGCA native tetramers and better substitutes than the very rare UGCG native tetramer. The correlation between in vivo and in vitro results suggests that in vitro assays measure parameters of in vivo relevance. Deletion of CUCGG247 (the 5' strand of stem-loop B) decreased the replicative capacity by more than 99.9% and metamorphosed the 3' DLS into an inhibitor of the loose dimerization of HIV-1 RNA.

Base Composition