Volume: 7, Issue: 4

Review

A Brief Review on the Mechanisms of miRNA Regulation

Yimei Cai, Xiaomin Yu, Songnian Hu, Jun Yu

MicroRNAs (miRNAs) are a class of short, endogenously-initiated non-coding RNAs that post-transcriptionally control gene expression via either translational repression or mRNA degradation. It is becoming evident that miRNAs are playing significant roles in regulatory mechanisms operating in various organisms, including developmental timing and host-pathogen interactions as well as cell differentiation, proliferation, apoptosis and tumorigenesis. Likewise, as a regulatory element, miRNA itself is coordinatively modulated by multifarious effectors when carrying out basic functions, such as SNP, miRNA editing, methylation and circadian clock. This mini-review summarized the current understanding of interactions between miRNAs and their targets, including recent advancements in deciphering the regulatory mechanisms that control the biogenesis and functionality of miRNAs in various cellular processes.

Page 147–154


Review Article

Nucleosomal Context of Binding Sites Influences Transcription Factor Binding Affinity and Gene Regulation

Zhiming Dai, Xianhua Dai, Qian Xiang, Jihua Feng

Transcription factor (TF) binding to its DNA target site plays an essential role in gene regulation. The location, orientation and spacing of transcription factor binding sites (TFBSs) also affect regulatory function of the TF. However, how nucleosomal context of TFBSs influences TF binding and subsequent gene regulation remains to be elucidated. Using genome-wide nucleosome positioning and TF binding data in budding yeast, we found that binding affinities of TFs to DNA tend to decrease with increasing nucleosome occupancy of the associated binding sites. We further demonstrated that nucleosomal context of binding sites is correlated with gene regulation of the corresponding TF. Nucleosome-depleted TFBSs are linked to high gene activity and low expression noise, whereas nucleosome-covered TFBSs are associated with low gene activity and high expression noise. Moreover, nucleosome-covered TFBSs tend to disrupt coexpression of the corresponding TF target genes. We conclude that nucleosomal context of binding sites influences TF binding affinity, subsequently affecting the regulation of TFs on their target genes. This emphasizes the need to include nucleosomal context of TFBSs in modeling gene regulation.

Page 155–162


Review Article

Significant Deviations in the Configurations of Homologous Tandem Repeats in Prokaryotic Genomes

Shintaro Hirayama, Satoshi Mizuta

We explored the possibilities of whole-genome duplication (WGD) in prokaryotic species, where we performed statistical analyses of the configurations of the central angles between homologous tandem repeats (TRs) on the circular chromosomes. At first, we detected TRs on their chromosomes and identified equivalent tandem repeat pairs (ETRPs); here, an ETRP is defined as a pair of tandem repeats sequentially similar to each other. Then we carried out statistical analyses of the central angle distributions of the detected ETRPs on each circular chromosome by way of comparisons between the detected distributions and those generated by null models. In the analyses, we estimated a P value by a simulation using the Kullback–Leibler divergence as a distance measure between two distributions. As a result, the central angle distributions for 8 out of the 203 prokaryotic species showed statistically significant deviations (P<0.05). In particular, we found out the characteristic feature of one round of WGD in Photorhabdus luminescens genome and that of two rounds of WGD in Escherichia coli K12.

Page 163–174


Review Article

Codon Usage Biases of Transposable Elements and Host Nuclear Genes in Arabidopsis thaliana and Oryza sativa

Jia Jia, Qingzhong Xue

Transposable elements (TEs) are mobile genetic entities ubiquitously distributed in nearly all genomes. High frequency of codons ending in A/T in TEs has been previously observed in some species. In this study, the biases in nucleotide composition and codon usage of TE transposases and host nuclear genes were investigated in the AT-rich genome of Arabidopsis thaliana and the GC-rich genome of Oryza sativa. Codons ending in A/T are more frequently used by TEs compared with their host nuclear genes. A remarkable positive correlation between highly expressed nuclear genes and C/G-ending codons were detected in O. sativa (r=0.944 and 0.839, respectively, P<0.0001) but not in A. thaliana, indicating a close association between the GC content and gene expression level in monocot species. In both species, TE codon usage biases are similar to that of weakly expressed genes. The expression and activity of TEs may be strictly controlled in plant genomes. Mutation bias and selection pressure have simultaneously acted on the TE evolution in A. thaliana and O. sativa. The consistently observed biases of nucleotide composition and codon usage of TEs may also provide a useful clue to accurately detect TE sequences in different species.

Page 175–184


Review Article

In Silico Characterization and Homology Modeling of Thylakoid-bound Ascorbate Peroxidase from a Drought Tolerant Wheat Cultivar

A. Katiyar, S.K. Lenka, K. Lakshmi, V. Chinnusamy, K.C. Bansal

Ascorbate peroxidase, a haem protein (EC 1.11.1.11), efficiently scavenges hydrogen peroxide (H2O2) in cytosol and chloroplasts of plants. In this study, a full-length coding sequence of thylakoid-bound ascorbate peroxidase cDNA (TatAPX) was cloned from a drought tolerant wheat cultivar C306. Homology modeling of the TatAPX protein was performed by using the template crystal structure of chloroplastic ascorbate peroxidase from tobacco plant (PDB: 1IYN). The model structure was further refined by molecular mechanics and dynamic methods using various tools such as PROCHECK, ProSA and Verify3D. The predicted model was then tested for docking with H2O2, the substrate for TatAPX enzyme. The results revealed that Arg233 and Glu255 in the predicted active site of the enzyme are two important amino acid residues responsible for strong hydrogen bonding affinity with H2O2, which might play an important role in scavenging of H2O2 from the plant system.

Page 185–193


Review Article

Large-Scale Analyses of Glycosylation in Cellulases

Fengfeng Zhou, Victor Olman, Ying Xu

Cellulases are important glycosyl hydrolases (GHs) that hydrolyze cellulose polymers into smaller oligosaccharides by breaking the cellulose β (1→4) bonds, and they are widely used to produce cellulosic ethanol from the plant biomass. N-linked and O-linked glycosylations were proposed to impact the catalytic efficiency, cellulose binding affinity and the stability of cellulases based on observations of individual cellulases. As far as we know, there has not been any systematic analysis of the distributions of N-linked and O-linked glycosylated residues in cellulases, mainly due to the limited annotations of the relevant functional domains and the glycosylated residues. We have computationally annotated the functional domains and glycosylated residues in cellulases, and conducted a systematic analysis of the distributions of the N-linked and O-linked glycosylated residues in these enzymes. Many N-linked glycosylated residues were known to be in the GH domains of cellulases, but they are there probably just by chance, since the GH domain usually occupies more than half of the sequence length of a cellulase. Our analysis indicates that the O-linked glycosylated residues are significantly enriched in the linker regions between the carbohydrate binding module (CBM) domains and GH domains of cellulases. Possible mechanisms are discussed.

Page 194–199


Method

A Modified Ant Colony Optimization Algorithm for Tumor Marker Gene Selection

Hualong Yu , Guochang Gu, Haibo Liu, Jing Shen, Jing Zhao

Microarray data are often extremely asymmetric in dimensionality, such as thousands or even tens of thousands of genes but only a few hundreds of samples or less. Such extreme asymmetry between the dimensionality of genes and samples can lead to inaccurate diagnosis of disease in clinic. Therefore, it has been shown that selecting a small set of marker genes can lead to improved classification accuracy. In this paper, a simple modified ant colony optimization (ACO) algorithm is proposed to select tumor-related marker genes, and support vector machine (SVM) is used as classifier to evaluate the performance of the extracted gene subset. Experimental results on several benchmark tumor microarray datasets showed that the proposed approach produces better recognition with fewer marker genes than many other methods. It has been demonstrated that the modified ACO is a useful tool for selecting marker genes and mining high dimension data.

Page 200–208