Vol 52, No 5 (2018)

HMGB proteins are involved in structural rearrangements caused by regulatory chromatin remodeling factors. Particular interest is attracted to a DNA chaperone mechanism, suggesting that the HMGB proteins introduce bends into the double helix, thus rendering DNA accessible to effector proteins and facilitating their activity. The review discusses the role that the HMBG proteins play in key intranuclear processes, including assembly of the preinitiation complex during transcription of ribosomal genes; transcription by RNA polymerases I, II, and III; recruitment of the SWI/SNF complex during transcription of nonribosomal genes; DNA repair; etc. The functions of the HMGB proteins are considered in detail with the examples of yeast HMO1 and NHP6. The two proteins possess unique features in adition to properties characteristic of the HMGB proteins. Thus, NHP6 stimulates a large-scale ATP-independent unwrapping of nucleosomal DNA by the FACT complex, while in its absence FACT stabilizes the nucleosome. HMO1 acts as an alternative linker histone. Both HMO1 and NHP6 are of applied interest primarly because they are homologs of human HMGB1, an important therapeutic target of anticancer and anti-inflammatory treatments.

Sumac is universally known for its abundance of raw lacquer. Toxicodendron vernicifluum (Stokes) F.A. Barkley is one of the widely distributed native sumac cultivars. To accelerate sumac breeding for more prolific, high-quality, and robust cultivars, it is essential to explore its lacquer metabolism. However, transcriptomic and genomic data available for sumac are still limited. In this study, we generated the transcriptomic profiles of triploid Toxicodendron vernicifluum CV. Dahongpao (Dahongpao) and diploid T. vernicifluum and Toxicodendron vernicifluum CV. Huoyanzi (Huoyanzi), with 87 856 unigenes. About 53% of these unigenes were annotated using Nr, Swiss-Prot, Kyoto Encyclopedia of Genes and Genomes (KEGG), Cluster of Orthologous Groups (COG) and Gene Ontology (GO). We identified nine differentially expressed candidate genes associated with type III polyketide synthase formation, which is the first step in urushiol biosynthesis. Additionally, a number of simple sequence repeats (EST–SSRs) were identified in T. vernicifluum for further molecular marker-assisted breeding. This study is the first report of Toxicodendron species transcriptome.

It is known that microRNAs (miRNAs) are able to dynamically regulate gene expression. At the same time, methylation can reduce expression of miRNA encoding genes and, therefore, reduce their inhibitory effects on mRNAs of target genes, including those of oncogenes, that promoting the development of tumors of different localization. The role of miRNA hypermethylation in the pathogenesis of ovarian cancer is not completely understood; so we conducted a search for new hypermethylated and potentially suppressor miRNA genes in ovarian tumors. Four new miRNA genes (MIR-107, MIR-130b, MIR-203a, MIR-1258) commonly hypermethylated (28‒52% ) in tumor tissues vs 4‒7% in paired histologically normal tissues, p < 0.01, were identified in a representative set of 54 ovarian cancer samples using methylation-specific PCR. It was shown that hypermethylation of MIR-130b, MIR-203a, and MIR-1258 genes is significantly (p ≤ 0.05) associated with metastasis of ovarian cancer. These results suggest the involvement of four miRNAs (miR-107, miR-130b, miR-203a, and miR-1258) and hypermethylation of their encoding genes in the pathogenesis of ovarian cancer.

The assembly of LIM-homeodomain (LIM-HD) transcriptional complex plays important roles in early neuronal development. The stability of LIM-HD is controlled by single-strand binding protein 3 (SSBP3) via a cascade mechanism protecting it from proteasomal degradation. The expression level of SSBP3 has to be precisely regulated. Although a decrease of SSBP3 level is associated with several diseases, the mechanism of SSBP3 downregulation and whether SSBP3 itself is subject to proteasomal degradation remain largely unknown. Two strongly conserved transcripts of the SSBP3 gene, SSBP3a and SSBP3c, were cloned from a human brain cDNA library. By RT-PCR, we show that Ssbp3c is continuously expressed in both embryonic and adult mouse brain, whereas Ssbp3a is restricted to embryonic brain tissue. By co-IP and GST pulldown assays, we identified SIVA1 as a novel SSBP3-binding factor. In a ubiquitination assay, we show that SIVA1 enhances the ubiquitination of SSBP3 and regulates its abundance. Our findings reveal the proteasomal degradation of SSBP3 for the first time and provide a rationale for an SIVA1-SSBP3-dependent mechanism for the disassembly of LIM-HD multiprotein complexes.

E-cadherin is a member of the cadherin family that plays a key role in the formation of cell-cell adhesion among epithelial tissues. Point mutations are one of the structural abnormalities of E-cadherin in human carcinomas. Such abnormalities can alter mechanical properties of proteins that play an important role in their biological activities. To determine the impact of point mutations on protein mechanical properties, the second fragment of extracellular domain of E-cadherin was modeled using steered molecular dynamics simulations. The molecular dynamics modeling included application of tensile forces in both constant velocity and constant force modes to examine the effects of Met282 to Ile and Asn315 to Ser mutations on mechanical behavior of protein structure. The stabilities of the wild type and mutant structures were also obtained by the protein design foldX algorithm. Results confirmed the lower stability of the mutant domains compared to the wild type. The mutated proteins displayed softer behavior than the reference protein and their stiffness decreased by up to 34%. Our findings suggest that local changes in molecular structure due to mutations may lead to noticeable alterations in mechanical properties within the entire domain. Since the function of protein is related to its structure, these changes may influence the function of the protein.

Increasing evidence has suggested that microRNAs (miRNAs) may function as positive regulators at the post-transcriptional level. A search for associations between miRNAs and diseases is crucial for understanding the pathogenesis. Various publicly available databases have been constructed to store meaningful information on a large number of miRNA molecules. In this study, to resolve the limitation that individual sources of miRNA target data tend to be incomplete and noisy, we propose a network-based computational method called self-weighting for integrating multiple data sources. A bipartite phenotype-miRNA network (BPMN) incorporates known disease–miRNA interactions as well as the similarities between disease phenotypes and functional similarities of miRNAs. Random walk with restart algorithm was deployed on the bipartite network to predict novel disease–miRNA associations. In leave-one-out cross-validation experiments, our technique achieves an AUC of 0.801 when evaluating against known disease-related miRNAs from HMDD. Systematic prioritization of miRNAs for 11 common diseases obtained an average AUC of 0.765. Additionally, a case study on colon cancer uncovered a number of potential miRNA candidates as biomarkers of this disease.