The membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) gene is associated with intellectual disability, early onset seizures, and autism spectrum disorders. This study aimed to determine the pathogenetic mechanism of the MBOAT7 missense variant via molecular modeling. Three patients from a consanguineous family were found to have a homozygous c.757G>A (p.Glu253Lys) variant of MBOAT7. The patients showed prominent dysfunction in gait, swallowing, vocalization, and fine motor function and had intellectual disabilities. Brain magnetic resonance imaging showed signal changes in the bilateral globus pallidi and cerebellar dentate nucleus, which differed with age. In the molecular model of human MBOAT7, Glu253 in the wild-type protein is located close to the backbone carbonyl oxygens in the loop near the helix, suggesting that the ionic interaction could contribute to the conformational stability of the funnel. Molecular modeling showed that Lys253 in the mutant protein was expected to alter the surface charge distribution, thereby potentially affecting substrate specificity. Changes in conformational stability and substrate specificity through varied ionic interactions are the suggested pathophysiological mechanisms of the MBOAT7 variant found in patients with intellectual disabilities.

Autophagy is a catabolic process through which cytoplasmic components are degraded and recycled in response to various stresses including starvation. Recently, transcriptional and epigenetic regulations of autophagy have emerged as essential mechanisms for maintaining homeostasis. Here, we identify that coactivator-associated arginine methyltransferase 1 (CARM1) methylates Pontin chromatin-remodeling factor under glucose starvation, and methylated Pontin binds Forkhead Box O 3a (FOXO3a). Genome-wide analyses and biochemical studies reveal that methylated Pontin functions as a platform for recruiting Tip60 histone acetyltransferase with increased H4 acetylation and subsequent activation of autophagy genes regulated by FOXO3a. Surprisingly, CARM1-Pontin-FOXO3a signaling axis can work in the distal regions and activate autophagy genes through enhancer activation. Together, our findings provide a signaling axis of CARM1-Pontin-FOXO3a and further expand the role of CARM1 in nuclear regulation of autophagy.

The discovery of novel drug targets of a genome that can bind with high affinity to drug-like compounds is a significant challenge in drug development. Streptococcus gordonii initiates dental plaque formation and endocarditis by entering into the blood stream, usually after oral trauma. The prolonged use of antibiotics is raising a problem of multi-drug resistance and lack of an optimal therapeutic regime that necessitates the drug discovery of vital importance in curing various infections. To overcome this dilemma, the in silico approach paves the way for identification and qualitative characterization of promising drug targets for S. gordonii that encompass three phases of analyses. The present study deciphers drug target genomes of S. gordonii in which 93 proteins were identified as potential drug targets and 16 proteins were found to be involved in unique metabolic pathways. Highlighted information will convincingly render to facilitate selection of S. gordonii proteins for successful entry into drug design pipelines.

Background: Although most nucleotides in the genome form canonical double-stranded B-DNA, many repeated sequences transiently present as non-canonical conformations (non-B DNA) such as triplexes, quadruplexes, Z-DNA, cruciforms, and slipped/hairpins. Those noncanonical DNAs (ncDNAs) are not only associated with many genetic events such as replication, transcription, and recombination, but are also related to the genetic instability that results in the predisposition to disease. Due to the crucial roles of ncDNAs in cellular and genetic functions, various computational methods have been implemented to predict sequence motifs that generate ncDNA. Objective: Here, we review strategies for the identification of ncDNA motifs across the whole genome, which is necessary for further understanding and investigation of the structure and function of ncDNAs. Conclusion: There is a great demand for computational prediction of non-canonical DNAs that play key functional roles in gene expression and genome biology. In this study, we review the currently available computational methods for predicting the non-canonical DNAs in the genome. Current studies not only provide an insight into the computational methods for predicting the secondary structures of DNA but also increase our understanding of the roles of non-canonical DNA in the genome.