Antisense transcription is a widespread phenomenon in mammalian genomes, leading to production of RNAs molecules referred to as natural antisense transcripts (NATs). NATs apply diverse transcriptional and post‐transcriptional regulatory mechanisms to carry out a wide variety of biological roles that are important for the normal functioning of living cells, but their dysfunctions can be associated with human diseases. In this review, we attempt to provide a molecular basis for the involvement of NATs in the etiology of human disorders such as cancers and neurodegenerative and cardiovascular diseases. We also discuss the pros and cons of oligonucleotide‐based therapies targeted against NATs, and we comment on state‐of‐the‐art progress in this promising area of clinical research. WIREs RNA 2018, 9:e1461. doi: 10.1002/wrna.1461This article is categorized under: RNA in Disease and Development > RNA in DiseaseRegulatory RNAs/RNAi/Riboswitches > Regulatory RNAsRNA Interactions with Proteins and Other Molecules > Small Molecule–RNA Interactions

Chromosomes occupy specific distinct areas in the nucleus of the sperm cell that may be altered in males with disrupted spermatogenesis. Here, we present alterations in the positioning of the human chromosomes 15, 18, X and Y between spermatozoa with the small supernumerary marker chromosome (sSMC; sSMC+) and spermatozoa with normal chromosome complement (sSMC−), for the first time described in the same ejaculate of an infertile, phenotypically normal male patient. Using classical and confocal fluorescent microscopy, the nuclear colocalization of chromosomes 15 and sSMC was analyzed. The molecular cytogenetic characteristics of sSMC delineated the karyotype as 47,XY,+der(15)(pter->p11.2::q11.1->q11.2::p11.2->pter)mat. Analysis of meiotic segregation showed a 1:1 ratio of sSMC+ to sSMC− spermatozoa, while evaluation of sperm aneuploidy status indicated an increased level of chromosome 13, 18, 21 and 22 disomy, up to 7 × (2.7 − 15.1). Sperm chromatin integrity assessment did not reveal any increase in deprotamination in the patient’s sperm chromatin. Importantly, we found significant repositioning of chromosomes X and Y towards the nuclear periphery, where both chromosomes were localized in close proximity to the sSMC. This suggests the possible influence of sSMC/XY colocalization on meiotic chromosome division, resulting in abnormal chromosome segregation, and leading to male infertility in the patient.

Long noncoding RNAs (lncRNAs) have emerged as prominent regulators of gene expression in eukaryotes. The identification of lncRNA orthologs is essential in efforts to decipher their roles across model organisms, as homologous genes tend to have similar molecular and biological functions. The relatively high sequence plasticity of lncRNA genes compared with protein-coding genes, makes the identification of their orthologs a challenging task. This is why comparative genomics of lncRNAs requires the development of specific and, sometimes, complex approaches. Here, we briefly review current advancements and challenges associated with four levels of lncRNA conservation: genomic sequences, splicing signals, secondary structures and syntenic transcription.

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A large portion of the human genome is transcribed into long noncoding RNAs that can range from 200 nucleotides to several kilobases in length. The number of identified lncRNAs is still growing, but only a handful of them have been functionally characterized. However, it is known that the functions of lncRNAs are closely related to their subcellular localization. Cytoplasmic lncRNAs can regulate mRNA stability, affect translation and act as miRNA sponges, while nuclear-retained long noncoding RNAs have been reported to be involved in transcriptional control, chromosome scaffolding, modulation of alternative splicing and chromatin remodelling. Through these processes, lncRNAs have diverse regulatory roles in cell biology and diseases. OIP5-AS1 (also known as Cyrano), a poorly characterized lncRNA expressed antisense to the OIP5 oncogene, is deregulated in multiple cancers. We showed that one of the OIP5-AS1 splicing forms (ENST00000501665.2) is retained in the cell nucleus where it associates with chromatin, thus narrowing down the spectrum of its possible mechanisms of action. Its knockdown with antisense LNA gapmeRs led to inhibited expression of a sense partner, OIP5, strongly suggesting a functional coupling between OIP5 and ENST00000501665.2. A subsequent bioinformatics analysis followed by RAP-MS and RNA Immunoprecipitation experiments suggested its possible mode of action; in particular, we found that ENST00000501665.2 directly binds to a number of nuclear proteins, including SMARCA4, a component of the SWI/SNF chromatin remodelling complex, whose binding motif is located in the promoter of the OIP5 oncogene.

Breast carcinogenesis is a multistep process that involves both genetic and epigenetic changes. Epigenetics refers to reversible changes in gene expression that are not accompanied by changes in gene sequence. In breast cancer (BC), dysregulated epigenetic changes, such as DNA methylation and histone modifications, are accompanied by epitranscriptomic changes, in particular adenine to inosine modifications within RNA molecules. Factors that trigger these phenomena are largely unknown, but there is evidence for widespread participation of long noncoding RNAs (lncRNAs) that already have been linked to virtually any aspect of BC biology, making them promising biomarkers and therapeutic targets in BC patients. Here, we provide a systematic review of known and possible roles of lncRNAs in epigenetic and epitranscriptomic processes, along with methods and tools to study them, followed by a brief overview of current challenges regarding the use of lncRNAs in medical applications.

Introduction: Robertsonian translocation (RobT) is the central fusion of the long arms of two acrocentric chromosomes, leading to 45 chromosomes in humans. The most common ones are rob(13;14) and rob(14;21) (91%). Other types of RobT are so-called rare cases. In the general population RobTs occur with a frequency of approximately 0.123%, but among men with reproductive failure this value rises 9-fold. Infertility in RobT carriers is associated with the formation of unbalanced spermatozoa resulting from segregation of the chromosomes involved in trivalent during the meiotic prophase. In spermatozoa of many RobT carriers an increased level of chromosomal aneuploidy is observed. Materials and Methods: We examined the hyperhaploidy level of chromosomes 7, 9, 18, 21, 22, X and Y in spermatozoa of 6 RobT unrelated carriers: two carriers with rare rob(13;15), one with rare rob(13;22), and three of the common rob(13;14). Results were compared with the control data from a group of 7 fertile men with a normal karyotype. Fluorescent in situ hybridization (FISH) was applied. Results: We found an increased level of sperm aneuploidy regarding at least one of the analyzed chromosomes in each of the carriers, while in rare RobTs interchromosomal effect (ICE) was observed. Meiotic segregation pattern of a rare rob(13;15) carrier revealed the 76% of normal /balanced spermatozoa. Disucussion: Due to the relatively high population frequency of RobTs, their influence on reproductive failure, hight risk of imbalancement in prenatal diagnosis (7%), and small amount of data for rare RobTs, each newly characterized case is valuable in genetic counseling.

Epitranscriptome refers to post-transcriptional modifications to RNA and their associated regulatory factors that can govern changes in an organism’s cells in response to various environmental stimuli. Recent studies have recognized over 170 distinct chemical signatures in RNA, and the list keeps expanding. These modifications are hypothesized to have roles beyond simply fine-tuning the structure and function of RNA, as studies have linked them to various infectious and noninfectious diseases in humans. Dedicated cellular machinery comprising of RNA-binding proteins (RBPs) that can write, erase, and read these modifications drives the regulation of the epitranscriptomic code, and as such influences RNA metabolism and homeostasis. Equally, perturbations in the function of RBPs may disrupt RNA processing, further implicating them in pathogenesis. As such, the mechanisms underlying RNA modifications and their association with RBPs are emerging areas of interest within the field of biomedicine. This review focuses on understanding epitranscriptomic modifications, their effects on RNA–RBPs interactions, and their influence on cellular processes.