Coupled nucleotide covariations reveal dynamic RNA interaction patterns

Gultyaev, Alexander P.; Franch, Thomas; Gerdes, Kenn

doi:10.1017/s1355838200990708

Cited by 16 publications

(9 citation statements)

References 56 publications

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“…In total, we scored 619× U and only 40× C for residue 31 when there is an A at position 22 (A22-U40 base pair), and only 3× U and 58× C when a G is present at position 22 (G22-U40 and G22-C40 base pairs). Such a coupled covariation between the residues at positions 22, 31, and 40 is indicative of either an alternative secondary structure in which the residues interact as mutually exclusive base pairs or of a base triple interaction (Gultyaev et al 2000). Using the Mfold program, we found no evidence for alternative secondary structures of TAR in which residues 22 and 31 interact directly (Zuker 1989;Mathews et al 1999;Zuker and Turner 1999).…”

Section: Comparative Sequence Analysis Suggests the Existence Of A Bamentioning

confidence: 79%

Evidence for a base triple in the free HIV-1 TAR RNA

Huthoff

Girard²,

Wijmenga³

et al. 2004

RNA

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We propose the existence of a novel base triple in the HIV-1 TAR hairpin. This triple is supported by covariation of loop residue 31 with residue 22, which is part of an unusual base pair with U40 below the 3-nucleotide bulge. A set of mutants was constructed to test the involvement of bases A22, U31, and U40 in a triple interaction. RNA structure probing, trans-activation assays, and structure modeling are consistent with the existence of this base triple in a bent conformation of the free TAR element. However, disruption of the base triple does not affect binding of a Tat-derived peptide. We therefore compared the structure of free and Tat-bound TAR RNA by footprinting and site-specific cross-linking analyses. These studies indicate that the Tat arginine-rich motif, in addition to its known binding site at the bulge, is in close contact with U31 in the TAR loop. Because binding of Tat to TAR is known to coincide with the formation of a base triple with residues U23, A27, and U38, we hypothesize that Tat binding and the associated straightening of TAR triggers the disruption of the (A22-U40)U31 triple.

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Section: Comparative Sequence Analysis Suggests the Existence Of A Bamentioning

confidence: 79%

Evidence for a base triple in the free HIV-1 TAR RNA

Huthoff

Girard²,

Wijmenga³

et al. 2004

RNA

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“…The existence of a few genetically homogeneous genetic groups suggests that the sequence space of these viruses may be restricted to a few narrow peaks in the adaptive or fitness landscape (Wright, 1932). A high level of covariation at molecular level (the coordinated change of certain nucleotides in response to the change of other nucleotides to maintain biologically relevant structures and functions) could explain this discontinuous adaptive landscape (Gultyaev et al, 2000). Reduced fitness of chimeras between CTV strains from different genetic subgroups occupying distinct adaptive peaks (Satyanarayana et al, 1999) support this notion.…”

Section: Discussionmentioning

confidence: 99%

Genetic variability and evolutionary dynamics of viruses of the family Closteroviridae

2013

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RNA viruses have a great potential for genetic variation, rapid evolution and adaptation. Characterization of the genetic variation of viral populations provides relevant information on the processes involved in virus evolution and epidemiology and it is crucial for designing reliable diagnostic tools and developing efficient and durable disease control strategies. Here we performed an updated analysis of sequences available in Genbank and reviewed present knowledge on the genetic variability and evolutionary processes of viruses of the family Closteroviridae. Several factors have shaped the genetic structure and diversity of closteroviruses. (I) A strong negative selection seems to be responsible for the high genetic stability in space and time for some viruses. (2) Long distance migration, probably by human transport of infected propagative plant material, have caused that genetically similar virus isolates are found in distant geographical regions. (3) Recombination between divergent sequence variants have generated new genotypes and plays an important role for the evolution of some viruses of the family Closteroviridae. (4) Interaction between virus strains or between different viruses in mixed infections may alter accumulation of certain strains. (5) Host change or virus transmission by insect vectors induced changes in the viral population structure due to positive selection of sequence variants with higher fitness for host-virus or vector-virus interaction (adaptation) or by genetic drift due to random selection of sequence variants during the population bottleneck associated to the transmission process.

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“…The coupled covariation pattern involving more than two bases (Fig. 2) is an indicator of a fine-tuned conformational transition (Gultyaev et al, 2000), and multiple examples of functionally important cotranscriptional RNA folding are known (Lai et al, 2013). Functional interchangeability of tetraloop types is usually explained by their exceptional stabilities (Sahu et al, 2012;Selinger et al, 1993;Uhlenbeck, 1990;Woese et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Tospovirus ambisense genomic RNA segments use almost complete repertoire of stable tetraloops in the intergenic region

2014

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Summary: The intergenic regions of the ambisense RNA segments of viruses from the Tospovirus genus form large extended RNA structures that regulate virus replication. Using comparative structure analysis, we show the presence of conserved alternative conformations at the apical parts of these structures. In one conformation, a branched Y-shape, the 5 0 -proximal hairpin arms are mostly capped by exceptionally stable tetraloop motifs. The tetraloop hairpins are folded in both virus and virus-complementary sense RNAs, and different tetraloops can functionally replace each other. Folding simulations show that the branched Y-shape structures can undergo a conformational transition to alternative extended rod-like conformations. Functional importance of both alternatives is supported by nucleotide covariations. The balanced equilibrium between alternative structures is evidenced by native gel electrophoresis of mutant RNA transcripts with shifted equilibria. The tetraloops play a role in the stability and dynamics of structures but may also be recognized by proteins involved in translation and/or replication.

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Coupled nucleotide covariations reveal dynamic RNA interaction patterns

Cited by 16 publications

References 56 publications

Evidence for a base triple in the free HIV-1 TAR RNA

Evidence for a base triple in the free HIV-1 TAR RNA

Genetic variability and evolutionary dynamics of viruses of the family Closteroviridae

Tospovirus ambisense genomic RNA segments use almost complete repertoire of stable tetraloops in the intergenic region

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