Conformational Preferences of Modified Nucleoside N(4)-Acetylcytidine, ac4C Occur at “Wobble” 34th Position in the Anticodon Loop of tRNA

Kumbhar, Bajarang Vasant; Kamble, Asmita S.; Sonawane, Kailas D.

doi:10.1007/s12013-013-9525-8

Cited by 55 publications

(47 citation statements)

References 71 publications

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“…The glycosyl torsion angle 'v' when allowed to change freely over the entire range 0-360°retained initial value (v = 28.7°), i.e., 'anti' conformation similar to crystal structure of tRNA Leu containing sm 5 U at 34th position [33], p-sm 5 U [32], lysidine (k 2 C) [55], Queuosine [34], and ac 4 C [56]. The 'anti' (v = 28.7°) conformation of glycosyl torsion angle would be useful to allow wobble 34th position sm 5 s 2 U atoms O(4), HN(3), and S(2) to interact with the last base of codons AAG/AAA all through protein biosynthesis process.…”

Section: Resultsmentioning

confidence: 78%

“…2) was used as a starting structure for the 5-ns molecular dynamics simulation study. MD simulation studies within 5-ns time period have been found valuable to appreciate the conformational preferences of modified nucleosides such as Que [34], ac 4 C [56], yW [42], OHyW [44], and m 2 G and m 2 2 G [70]. The results of analyzed average (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…6) with the help of Spartan ver 6.0.1 software [35] as calculated for the base pair model of sm 5 U 34 :G 3 [32], ac 4 C(Proximal/Distal) 34 :G 3 /A 3 [56]. The color scale range of sm 5 s 2 U 34 :G 3 base pair model is in between -6.5 Min to 2.2 Max V. The MEPs show three distinct potential tunnels between hydrogen bond donor and acceptor atoms of sm 5 s 2 U 34 :G 3 model (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…8a) have been carried out using semiempirical RM1 method to get the overall idea about the conformational space of sm 5 s 2 U similar to earlier studies [32,56,80]. The initial torsion angle values for sm 5 s 2 U (34) have been utilized from the side chain of RM1 preferred most stable conformation of 'p-sm 5 s 2 U' as shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Conformational energy calculations have been performed to understand the structural significance of various hypermodified nucleosides, for example lysidine, k 2 C [55], N(4)-acetylcytidine, ac 4 C [56], queuosine [34] present at 'wobble' (34th) position and modifications present at '3'-adjacent' (37th) position together with their protonation effect such as wybutine (yW) and hydroxywybutine (OHyW) [42,44], t 6 Ade, g 6 Ade [57,58], i 6 Ade and ms 2 i 6 Ade [59], cis-io 6 Ade, trans-io 6 Ade, cis-ms 2 io 6 Ade and trans-ms 2 io 6 Ade [60], gc 6 Ade [61], tc 6 Ade [62] as well as m 2 G and m 2 2 G which occur at the tRNA hinge region of tRNA [43].…”

Section: Methodsmentioning

confidence: 99%

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Structural significance of modified nucleoside 5-taurinomethyl-2-thiouridine, τm5s2U, found at ‘wobble’ position in anticodon loop of human mitochondrial tRNALys

et al. 2015

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The myoclonus epilepsy associated with ragged-red fibers (MERRF) is a mitochondrial encephalomyopathic disease caused due to the lack of hypermodified nucleoside 5-taurinomethyl-2-thiouridine at 'wobble' 34th position in the anticodon loop of human mitochondrial tRNA Lys . Understanding the structural significance of sm 5 s 2 U might be helpful to get more information about the MERRF disease in detail at the atomic level. Hence, conformational preferences of hypermodified nucleoside 5-taurinomethyl-2-thiouridine 5 0 -monophosphate, 'p-sm 5 s 2 U,' have been studied using semiempirical quantum chemical RM1 method. Full geometry optimization using ab initio molecular orbital HF-SCF (6-31G**) and DFT (B3LYP/6-31G**) methods has also been used to compare the salient features. The RM1 preferred most stable conformation of 'p-sm 5 s 2 U' has been stabilized by hydrogen bonding interactions between O(11a)…HN (8), O1P (34) … HN(8), O1P (34) …HC(10), O4 0 (34) …HC(6), S(2)…HC1 0 (34), O5 0 (34) …HC(6), and O(4)…HC (7). Another conformational study of 5-taurinomethyl-2-thiouridine side chain in the presence of anticodon loop bases of human mitochondrial tRNA Lys showed similar conformation as found in RM1 preferred most stable conformation of 'p-sm 5 s 2 U.' The glycosyl torsion angle of sm 5 s 2 U retains 'anti' conformation. Similarly, MD simulation results are also found in accordance with RM1 preferred stable structure. The solvent-accessible surface area calculations revealed surface accessibility of sm 5 s 2 U in human mt tRNA Lys anticodon loop. The MEPs calculations of codon-anticodon models of sm 5 s 2 U (34) :G 3 and sm 5 s 2 U (34) :A 3 showed unique potential tunnels between the hydrogen bond donor and acceptor atoms. These results might be useful to understand the exact role of sm 5 s 2 U (34) to recognize AAG/ AAA codons and to design new strategies to prevent mitochondrial disease, MERRF.

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Section: Resultsmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Structural significance of modified nucleoside 5-taurinomethyl-2-thiouridine, τm5s2U, found at ‘wobble’ position in anticodon loop of human mitochondrial tRNALys

et al. 2015

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Beyond reader proteins: RNA binding proteins and RNA modifications in conversation to regulate gene expression

Fagre,

Gilbert

2024

WIREs RNA

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Post‐transcriptional mRNA modifications play diverse roles in gene expression and RNA function. In many cases, RNA modifications function by altering how cellular machinery such as RNA binding proteins (RBPs) interact with RNA substrates. For instance, N6‐methyladenosine (m6A) is recognized by the well‐characterized YTH domain‐containing family of “reader” proteins. For other mRNA modifications, similar global readers of modification status have not been clearly defined. Rather, most interactions between RBPs and RNA modifications have a more complicated dependence on sequence context and binding modality. The current handful of studies that demonstrate modifications impacting protein binding likely represent only a fraction of the full landscape. In this review, we dissect the known instances of RNA modifications altering RBP binding, specifically m6A, N1‐methyladenosine (m1A), 5‐methylcytosine (m5C), pseudouridine (Ψ), and internal N7‐methylguanosine. We then review the biochemical properties of these and other identified mRNA modifications including dihydrouridine (D), N4‐acetylcytosine (ac4C), and 2′‐O‐Methylation (Nme). We focus on how these properties would be likely to impact RNA:RBP interactions, including by changes to hydrogen bond potential, base‐stacking efficiency, and RNA conformational preferences. The effects of RNA modifications on secondary structure have been well‐studied, and we briefly discuss how structural effects imparted by modifications can lead to protein binding changes. Finally, we discuss strategies for uncovering as‐yet‐to‐be identified modification‐sensitive RBP:RNA Interactions. Coordinating future efforts to intersect the epitranscriptome and the RNA–protein interactome will illuminate the rules governing RNA modification recognition and the mechanisms responsible for the biological consequences of mRNA modification.This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Interactions with Proteins and Other Molecules > Protein‐RNA Recognition RNA Processing > RNA Editing and Modification

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Chemical Modifications of Ribosomal RNA

Sharma

Entian

2022

Ribosome Biogenesis

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Cellular RNAs in all three kingdoms of life are modified with diverse chemical modifications. These chemical modifications expand the topological repertoire of RNAs, and fine-tune their functions. Ribosomal RNA in yeast contains more than 100 chemically modified residues in the functionally crucial and evolutionary conserved regions. The chemical modifications in the rRNA are of three types—methylation of the ribose sugars at the C2-positionAbstract (Nm), isomerization of uridines to pseudouridines (Ψ), and base modifications such as (methylation (mN), acetylation (acN), and aminocarboxypropylation (acpN)). The modifications profile of the yeast rRNA has been recently completed, providing an excellent platform to analyze the function of these modifications in RNA metabolism and in cellular physiology. Remarkably, majority of the rRNA modifications and the enzymatic machineries discovered in yeast are highly conserved in eukaryotes including humans. Mutations in factors involved in rRNA modification are linked to several rare severe human diseases (e.g., X-linked Dyskeratosis congenita, the Bowen–Conradi syndrome and the William–Beuren disease). In this chapter, we summarize all rRNA modifications and the corresponding enzymatic machineries of the budding yeast.

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Conformational Preferences of Modified Nucleoside N(4)-Acetylcytidine, ac4C Occur at “Wobble” 34th Position in the Anticodon Loop of tRNA

Cited by 55 publications

References 71 publications

Structural significance of modified nucleoside 5-taurinomethyl-2-thiouridine, τm5s2U, found at ‘wobble’ position in anticodon loop of human mitochondrial tRNALys

Structural significance of modified nucleoside 5-taurinomethyl-2-thiouridine, τm5s2U, found at ‘wobble’ position in anticodon loop of human mitochondrial tRNALys

Beyond reader proteins: RNA binding proteins and RNA modifications in conversation to regulate gene expression

Chemical Modifications of Ribosomal RNA

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