DNA methylation and histone modifications are essential for regulation of stem cell formation and differentiation in zebrafish development

The complex processes necessary for embryogenesis require a gene regulatory network that is complex and systematic. Gene expression regulates development and organogenesis, but this process is altered and fine-tuned by epigenetic regulators that facilitate changes in the chromatin landscape. Epigenetic regulation of embryogenesis adjusts the chromatin structure by modifying both DNA through methylation and nucleosomes through posttranslational modifications of histone tails. The zebrafish is a well-characterized model organism that is a quintessential tool for studying developmental biology. With external fertilization, low cost and high fecundity, the zebrafish are an efficient tool for studying early developmental stages. Genetic manipulation can be performed in vivo resulting in quick identification of gene function. Large-scale genome analyses including RNA sequencing, chromatin immunoprecipitation and chromatin structure all are feasible in the zebrafish. In this review, we highlight the key events in zebrafish development where epigenetic regulation plays a critical role from the early stem cell stages through differentiation and organogenesis.

Functional long non-coding and circular RNAs in zebrafish

The utility of model organisms to understand the function of a novel transcript/genes has allowed us to delineate their molecular mechanisms in maintaining cellular homeostasis. Organisms such as zebrafish have contributed a lot in the field of developmental and disease biology. Attributable to advancement and deep transcriptomics, many new transcript isoforms and non-coding RNAs such as long noncoding RNA (lncRNA) and circular RNAs (circRNAs) have been identified and cataloged in multiple databases and many more are yet to be identified. Various methods and tools have been utilized to identify lncRNAs/circRNAs in zebrafish using deep sequencing of transcriptomes as templates. Functional analysis of a few candidates such as tie1-AS, ECAL1 and CDR1as in zebrafish provides a prospective outline to approach other known or novel lncRNA/circRNA. New genetic alteration tools like TALENS and CRISPRs have helped in probing for the molecular function of lncRNA/circRNA in zebrafish. Further latest improvements in experimental and computational techniques offer the identification of lncRNA/circRNA counterparts in humans and zebrafish thereby allowing easy modeling and analysis of function at cellular level.

Identification of long noncoding RNAs with machine learning methods: a review

Long noncoding RNAs (lncRNAs) are noncoding RNAs with a length greater than 200 nucleotides. Studies have shown that they play an important role in many life activities. Dozens of lncRNAs have been characterized to some extent, and they are reported to be related to the development of diseases in a variety of cells. However, the biological functions of most lncRNAs are currently still unclear. Therefore, accurately identifying and predicting lncRNAs would be helpful for research on their biological functions. Due to the disadvantages of high cost and high resource-intensiveness of experimental methods, scientists have developed numerous computational methods to identify and predict lncRNAs in recent years. In this paper, we systematically summarize the machine learning-based lncRNAs prediction tools from several perspectives, and discuss the challenges and prospects for the future work.

Integrative analyses of transcriptome data reveal the mechanisms of post-transcriptional regulation

Post-transcriptional processing of RNAs plays important roles in a variety of physiological and pathological processes. These processes can be precisely controlled by a series of RNA binding proteins and cotranscriptionally regulated by transcription factors as well as histone modifications. With the rapid development of high-throughput sequencing techniques, multiomics data have been broadly used to study the mechanisms underlying the important biological processes. However, how to use these high-throughput sequencing data to elucidate the fundamental regulatory roles of post-transcriptional processes is still of great challenge. This review summarizes the regulatory mechanisms of post-transcriptional processes and the general principles and approaches to dissect these mechanisms by integrating multiomics data as well as public resources.

The non-coding epitranscriptome in cancer

Post-synthesis modification of biomolecules is an efficient way of regulating and optimizing their functions. The human epitranscriptome includes a variety of more than 100 modifications known to exist in all RNA subtypes. Modifications of non-coding RNAs are particularly interesting since they can directly affect their structure, stability, interaction and function. Indeed, non-coding RNAs such as tRNA and rRNA are the most modified RNA species in eukaryotic cells. In the last 20 years, new functions of non-coding RNAs have been discovered and their involvement in human disease, including cancer, became clear. In this review, we will present the evidence connecting modifications of different non-coding RNA subtypes and their role in cancer.

Flipping the script: viral capitalization of RNA modifications

RNA encoded by RNA viruses is highly regulated so that it can function in multiple roles during the viral life cycle. These roles include serving as the mRNA template for translation or the genetic material for replication as well as being packaged into progeny virions. RNA modifications provide an emerging regulatory dimension to the RNA of viruses. Modification of the viral RNA can increase the functional genomic capacity of the RNA viruses without the need to encode and translate additional genes. Further, RNA modifications can facilitate interactions with host or viral RNA-binding proteins that promote replication or can prevent interactions with antiviral RNA-binding proteins. The mechanisms by which RNA viruses facilitate modification of their RNA are diverse. In this review, we discuss some of these mechanisms, including exploring the unknown mechanism by which the RNA of viruses that replicate in the cytoplasm could acquire the RNA modification N6-methyladenosine.