The three-dimensional architecture of the class I ligase ribozyme

Bergman, Nicholas H.; Lau, Nelson C.; Lehnert, Valerie; Westhof, Éric; Bartel, David P.

doi:10.1261/rna.5177504

Cited by 46 publications

(44 citation statements)

References 37 publications

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“…One explanation for this is that the starting B16-19 ligase was highly adapted and is likely in a strong local fitness optimum (Lehman 2004). In fact, if the secondary structure in Figure 2 is correct, then less than half of the ligase's nucleotides are not base paired (62 of 135), and some of these are involved in tertiary contacts (Bergman et al 2004). Thus relatively little of the molecule is actually free to tolerate mildly deleterious mutations; all of the ones that we did see lay in non-basepaired regions ( Figure 2B).…”

Section: Resultsmentioning

confidence: 99%

Accumulation of Deleterious Mutations in Small Abiotic Populations of RNA

Soll¹,

Arenas

Lehman

2007

Genetics

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The accumulation of slightly deleterious mutations in populations leads to the buildup of a genetic load and can cause the extinction of populations of small size. Mutation-accumulation experiments have been used to study this process in a wide variety of organisms, yet the exact mutational underpinnings of genetic loads and their fitness consequences remain poorly characterized. Here, we use an abiotic system of RNA populations evolving continuously in vitro to examine the molecular events that can instigate a genetic load. By tracking the fitness decline of ligase ribozyme populations with bottleneck sizes between 100 and 3000 molecules, we detected the appearance and subsequent fixation of both slightly deleterious mutations and advantageous mutations. Smaller populations went extinct in significantly fewer generations than did larger ones, supporting the notion of a mutational meltdown. These data suggest that mutation accumulation was an important evolutionary force in the prebiotic RNA world and that mechanisms such as recombination to ameliorate genetic loads may have been in place early in the history of life.

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Section: Resultsmentioning

confidence: 99%

Accumulation of Deleterious Mutations in Small Abiotic Populations of RNA

Soll¹,

Arenas

Lehman

2007

Genetics

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“…Indeed, classic work with sources tethered to single residues of transfer RNA, ribosomes, and other non-coding RNAs calibrated the relationship of RNA backbone cleavage with distance and established the utility of these data for nucleotide-resolution RNA and RNA-protein modeling (see, e.g. Bergman et al 2004;Culver & Noller, 2000;Han & Dervan, 1994;Lancaster et al 2002). The reliability of pairwise constraints from tethered radical source experiments has been further supported by comparison of these and other types of biochemical data on the ribosome with subsequently solved crystal structures (Sergiev et al 2001;Whirl-Carrillo et al 2002).…”

Section: Precedents For Pairwise Data From Tethered Radical Cleavagementioning

confidence: 99%

RNA structure through multidimensional chemical mapping

Tian

Das

2016

Quart. Rev. Biophys.

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Abstract. The discoveries of myriad non-coding RNA molecules, each transiting through multiple flexible states in cells or virions, present major challenges for structure determination. Advances in high-throughput chemical mapping give new routes for characterizing entire transcriptomes in vivo, but the resulting one-dimensional data generally remain too information-poor to allow accurate de novo structure determination. Multidimensional chemical mapping (MCM) methods seek to address this challenge. Mutate-and-map (M 2 ), RNA interaction groups by mutational profiling (RING-MaP and MaP-2D analysis) and multiplexed •OH cleavage analysis (MOHCA) measure how the chemical reactivities of every nucleotide in an RNA molecule change in response to modifications at every other nucleotide. A growing body of in vitro blind tests and compensatory mutation/rescue experiments indicate that MCM methods give consistently accurate secondary structures and global tertiary structures for ribozymes, ribosomal domains and ligand-bound riboswitch aptamers up to 200 nucleotides in length. Importantly, MCM analyses provide detailed information on structurally heterogeneous RNA states, such as ligand-free riboswitches that are functionally important but difficult to resolve with other approaches. The sequencing requirements of currently available MCM protocols scale at least quadratically with RNA length, precluding general application to transcriptomes or viral genomes at present. We propose a modify-cross-link-map (MXM) expansion to overcome this and other current limitations to resolving the in vivo 'RNA structurome'.

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“…In contrast, solution HRP, which reports the approximate backbone solvent accessibility for most nucleotides in an RNA molecule (Cate et al, 1996;Tullius and Greenbaum, 2005), is straightforward to implement. HRP measurements have been used to evaluate or filter RNA structural ensembles (Bergman et al, 2004;Jonikas et al, 2009;Rangan et al, 2003;Tullius and Greenbaum, 2005) but have not been used to drive RNA 3D structure determination in a quantitative and systematic way. We developed an approach that incorporates solvent accessibility information derived from HRP measurements to bias DMD (Dokholyan et al, 1998;Zhou and Karplus, 1997) simulations in order to generate structural ensembles consistent with experimental measurements.…”

Section: Solvent Accessibilitymentioning

confidence: 99%