scholarly journals Structural Diversity and Phylogenetic Distribution of Valyl tRNA-like Structures in Viruses

Author(s):  
Madeline E. Sherlock ◽  
Erik W. Hartwick ◽  
Andrea MacFadden ◽  
Jeffrey S. Kieft

ABSTRACTViruses commonly use specifically folded RNA elements that interact with both host and viral proteins to perform functions important for diverse viral processes. Examples are found at the 3′ termini of certain positive-sense ssRNA virus genomes where they partially mimic tRNAs, including being aminoacylated by host cell enzymes. Valine-accepting tRNA-like structures (TLSVal) are an example that share some clear homology to canonical tRNAs but have several important structural differences. Although many examples of TLSVal have been identified, we lacked a full understanding of their structural diversity and phylogenetic distribution. To address this, we undertook an in-depth bioinformatic and biochemical investigation of these RNAs, guided by recent high-resolution structures of a TLSVal. We cataloged many new examples in plant-infecting viruses but also in unrelated insect-specific viruses. Using biochemical and structural approaches, we verified the secondary structure of representative TLSVal substrates and tested their ability to be valylated, finding structural heterogeneity within this class. In a few cases, large stem-loop structures are inserted within distinct variable regions located in an area of the TLS distal to known host cell factor binding sites. In addition, we identified one virus whose TLS has switched its anticodon away from valine; the implications of this remain unclear. These results refine our understanding of the structural and functional mechanistic details of tRNA mimicry and how this may be used in viral infection.

2013 ◽  
Vol 4 (1) ◽  
pp. 2 ◽  
Author(s):  
Wayne Dawson ◽  
Kenji Yamamoto ◽  
Kentaro Shimizu ◽  
Gota Kawai

In previous work, we have shown that the entropy of a folded RNA molecule can be divided into local and global contributions using the cross-linking entropy (CLE) model, where, in the case of RNA, the cross- links are the base-pair stacking interactions. The local contribution to the CLE is revealed in the Kuhn length (a measure of the stiffness of the RNA). The Kuhn length acts as a scaling parameter. When the size of the system is rescaled, the relationship between local and global free energy must be renormalized to reflect this rescaling. In this renormalization process, the Kuhn length increases, the local entropy also increases due to freezing out of the local conformational degrees of freedom. At the same time, as the number of degrees of freedom decrease, there is a significant reduction in the global entropy. Here we present a method, based on the concepts of renormalization theory, to quantitatively estimate the size of the contribution from the local entropy as a function of the Kuhn length. The local entropy correction is used to predict the current empirically derived constant in the Jacobson-Stockmayer equation. The variation in the Kuhn length is shown to be largely influenced by the length of the double-stranded RNA stems formed in the secondary structure of folded RNA. This result is used to test the resulting entropy under a variable Kuhn length in stem-loop structures. Comparisons between a variable Kuhn length and a static Kuhn length on a short stem-loop of RNA are also examined. The model is quite general and is also directly applicable to protein structure and folding problems.


Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 356 ◽  
Author(s):  
David Balgoma ◽  
Luis Gil-de-Gómez ◽  
Olimpio Montero

The pathogenic mechanisms underlying the Biology and Biochemistry of viral infections are known to depend on the lipid metabolism of infected cells. From a lipidomics viewpoint, there are a variety of mechanisms involving virus infection that encompass virus entry, the disturbance of host cell lipid metabolism, and the role played by diverse lipids in regard to the infection effectiveness. All these aspects have currently been tackled separately as independent issues and focused on the function of proteins. Here, we review the role of cholesterol and other lipids in ssRNA+ infection.


RNA ◽  
2020 ◽  
Vol 27 (1) ◽  
pp. 27-39
Author(s):  
Madeline E. Sherlock ◽  
Erik W. Hartwick ◽  
Andrea MacFadden ◽  
Jeffrey S. Kieft

2015 ◽  
Vol 45 (11) ◽  
pp. 1448-1461 ◽  
Author(s):  
Christian Kuehne ◽  
Aaron R. Weiskittel ◽  
Shawn Fraver ◽  
Klaus J. Puettmann

Thinning is believed to accelerate the development of late-successional attributes, thereby enhancing stand structural heterogeneity in young, secondary forests. By making use of a large-scale experiment implemented in 40- to 60-year-old coastal Douglas-fir (Pseudotsuga menziesii (Mirbel) Franco) forests, we addressed the following objectives: (i) determine the effect of three thinning treatments on the temporal dynamics (first 11 years after thinning) of key forest structure measures, (ii) evaluate the relationships between spatially explicit structural diversity measures and spatially nonexplicit stand metrics, and (iii) test the relationships between stand structure and observed periodic stand volume growth, ingrowth, and mortality. Treatments consisted of high-density, moderate-density, and variable-density thinnings-from-below, as well as a control. Differences in stand structural heterogeneity between treatments were mostly nonsignificant. However, our results suggest that variable-density stands displayed structural enrichment as tree size and tree species diversity increased throughout the study period as a result of continuous ingrowth of species other than Douglas-fir. Simple spatially nonexplicit metrics could not be used to reliably model spatially explicit structural diversity measures. The inclusion of structural and species diversity measures only rarely improved accuracy of sample plot level growth, ingrowth, and mortality prediction models. Despite the short-term nature of this study, we conclude that variable-density thinning shows promise in increasing structural heterogeneity in young even-aged stands. The inclusion of structural diversity measures in growth and mortality models may be beneficial, but further work is needed to clarify the underlying relationships, particularly at the individual-tree level.


2016 ◽  
Vol 14 (01) ◽  
pp. 1650006
Author(s):  
Cong Pian ◽  
Jin Zhang ◽  
Yuan-Yuan Chen ◽  
Zhi Chen ◽  
Qin Li ◽  
...  

MicroRNAs (miRNAs) are a set of short (21–24 nt) non-coding RNAs that play significant regulatory roles in the cells. Triplet-SVM-classifier and MiPred (random forest, RF) can identify the real pre-miRNAs from other hairpin sequences with similar stem-loop (pseudo pre-miRNAs). However, the 32-dimensional local contiguous structure-sequence can induce a great information redundancy. Therefore, it is essential to develop a method to reduce the dimension of feature space. In this paper, we propose optimal features of local contiguous structure-sequences (OP-Triplet). These features can avoid the information redundancy effectively and decrease the dimension of the feature vector from 32 to 8. Meanwhile, a hybrid feature can be formed by combining minimum free energy (MFE) and structural diversity. We also introduce a neural network algorithm called extreme learning machine (ELM). The results show that the specificity ([Formula: see text])and sensitivity ([Formula: see text]) of our method are 92.4% and 91.0%, respectively. Compared with Triplet-SVM-classifier, the total accuracy (ACC) of our ELM method increases by 5%. Compared with MiPred (RF) and miRANN, the total accuracy (ACC) of our ELM method increases nearly by 2%. What is more, our method commendably reduces the dimension of the feature space and the training time.


2021 ◽  
Author(s):  
ZHONGHUA ZHAO ◽  
Gongqiao Zhang ◽  
Wenzhen Liu ◽  
Gangying Hui ◽  
Ganggang Zhang ◽  
...  

Abstract Background Improving the diversity and complexity of stand structure is the basis for maintaining and increasing forest ecosystem biodiversity. Measures of stand structural diversity is important for predicting stand growth and evaluating forest management activities. Based on the relationship of adjacent trees, we present a new method for the quantitative analysis of stand structure diversity that allows comparison of stand structural heterogeneity between different stands and forest types and to quantify the impact of forest management on structural diversity. Method: The diversity of structural unit types was defined and then we derive a new index of forest structural diversity () according to the additivity principle of Shannon-Weiner index. The effectiveness and sensitivity to management were verified by sixteen field survey samples in different locations and six different simulated management datasets based on Pinus koraiensis broad-leaved forest survey sample. Results (1) The mountain rainforest in Hainan had the highest \({{S}^{\text{'}}}_{D}\) value at 5.287, followed by broad-leaved Korean pine forest in Jiaohe (2), Jiaohe (1) and oak broadleaved mixed natural forest in Xiaolongshan (2), with values of 5.144, 5.014 and 5.006, respectively. The \({{S}^{\text{'}}}_{D}\) values of plantations and natural pure forest were lower. (2) Different thinning methods and intensities reduced \({{S}^{\text{'}}}_{D}\) compared with no treatment and magnitude of the with the differences were greater as thinning intensity increased. The \({{S}^{\text{'}}}_{D}\) value of thinning from above decreased more than thinning from below at the same thinning intensity. Conclusion The\({{S}^{\text{'}}}_{D}\) well describes differences in stand structural diversity of different forest types and allows comparison of stand structural heterogeneity. It is also sensitive to forest management activities and to quantify the impact of forest management on structural diversity. The application of this new index \({{S}^{\text{'}}}_{D}\) could greatly facilitate forest management and monitoring.


1991 ◽  
Vol 174 (3) ◽  
pp. 613-624 ◽  
Author(s):  
S E Stark ◽  
A J Caton

We have analyzed how the immune system generates antibodies that are specific for analogues of an epitope on the influenza virus hemagglutinin (HA) that differ solely by the presence of Asp or Gly at amino acid 225. Most antibodies induced in response to HA(Asp225) use one of a few closely related variable (V) region structures that are encoded by characteristic VH/Vk gene segment combinations. Remarkably, none of these VH/Vk combinations was induced in response to HA(Gly225). Instead of modifying the HA(Asp225)-specific V regions by junctional variation or somatic mutation to recognize the altered epitope, new VH/Vk combinations were used. The expression of unique VH/Vk combinations appears to confer exquisite specificity to the selection of HA-specific B cells from the pre-immune repertoire.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chuan Ma ◽  
Yeying Wang ◽  
Licui Zhang ◽  
Jianke Li

AbstractThe Trigonidiidae, a family of crickets, comprises 981 valid species with only one mitochondrial genome (mitogenome) sequenced to date. To explore mitogenome features of Trigonidiidae, six mitogenomes from its two subfamilies (Nemobiinae and Trigonidiinae) were determined. Two types of gene rearrangements involving a trnN-trnS1-trnE inversion and a trnV shuffling were shared by Trigonidiidae. A long intergenic spacer was observed between trnQ and trnM in Trigonidiinae (210−369 bp) and Nemobiinae (80–216 bp), which was capable of forming extensive stem-loop secondary structures in Trigonidiinae but not in Nemobiinae. The anticodon of trnS1 was TCT in Trigonidiinae, rather than GCT in Nemobiinae and other related subfamilies. There was no overlap between nad4 and nad4l in Dianemobius, as opposed to a conserved 7-bp overlap commonly found in insects. Furthermore, combined comparative analysis and transcript verification revealed that nad1 transcripts ended with a U, corresponding to the T immediately preceding a conserved motif GAGAC in the superfamily Grylloidea, plus poly-A tails. The resultant UAA served as a stop codon for species lacking full stop codons upstream of the motif. Our findings gain novel understanding of mitogenome structural diversity and provide insight into accurate mitogenome annotation.


2015 ◽  
Vol 90 (6) ◽  
pp. 2971-2980 ◽  
Author(s):  
Leonardo Valdivieso-Torres ◽  
Anindita Sarangi ◽  
Jillian Whidby ◽  
Joseph Marcotrigiano ◽  
Monica J. Roth

ABSTRACTRetargeting of gammaretroviral envelope proteins has shown promising results in the isolation of novel isolates with therapeutic potential. However, the optimal conditions required to obtain high-affinity retargeted envelope proteins with narrow tropism are not understood. This study highlights the advantage of constrained peptides within receptor binding domains and validates the random library screening technique of obtaining novel retargeted Env proteins. Using a modified vector backbone to screen the envelope libraries on 143B osteosarcoma cells, three novel and unique retargeted envelopes were isolated. The use of complex disulfide bonds within variable regions required for receptor binding is found within natural gammaretroviral envelope isolates. Interestingly, two of the isolates, named AII and BV2, have a pair of cysteines located within the randomized region of 11 amino acids similar to that identified within the CP Env, an isolate identified in a previous Env library screen on the human renal carcinoma Caki-1 cell line. The amino acids within the randomized region of AII and BV2 envelopes that are essential for viral infection have been identified in this study and include these cysteine residues. Through mutagenesis studies, the putative disulfide bond pairs including and beyond the randomized region were examined. In parallel, the disulfide bonds of CP Env were identified using mass spectrometry. The results indicate that this pair of cysteines creates the structural context to position key hydrophobic (F and W) and basic (K and H) residues critical for viral titer and suggest that AII, BV2, and CP internal cysteines bond together in distinct ways.IMPORTANCERetargeted gammaretroviral particles have broad applications for therapeutic use. Although great advances have been achieved in identifying new Env-host cell receptor pairs, the rules for designing optimal Env libraries are still unclear. We have found that isolates with an additional pair of cysteines within the randomized region have the highest transduction efficiencies. This emphasizes the importance of considering cysteine pairs in the design of new libraries. Furthermore, our data clearly indicate that these cysteines are essential for viral infectivity by presenting essential residues to the host cell receptor. These studies facilitate the screening of Env libraries for functional entry into target cells, allowing the identification of novel gammaretroviral Envs targeting alternative host cell receptors for gene and protein delivery.


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