Search bioRxiv⌕ Search

bioRxiv · 10.1101/2020.02.08.940148

Antisense ncRNAs during early vertebrate development are divided in groups with distinct features

Abstract

Long non-coding RNAs or lncRNAs are a broad class of non-protein coding RNAs that are >200nucleotides in length. A number of lncRNAs are shown to play an important role in gene expression regulation. LncRNAs antisense to a protein-coding gene can act either as positive or negative regulators of overlapping protein-coding mRNAs. Almost 50% of lncRNAs present during development of vertebrates such as zebrafish are of antisense lncRNA class. However, their role in gene expression regulation during development remains enigmatic. To understand the role of antisense lncRNAs in early vertebrate development, we took a computational biology approach to analyze existing as well as novel dataset. Our analysis of RNA sequencing data from zebrafish development indicates that antisense RNAs can be divided into two major classes based on their positive or negative co-expression patterns to the sense protein-coding genes. The ones with negative co-expression patterns or group-1 are maternal antisense lncRNAs that overlap mainly developmental genes. Group-2 with positive expression pattern overlap mainly house-keeping genes. Group-1 antisense lncRNAs are longer and more stable as compared to antisense lncRNAs in group-2. In addition, to answer if antisense RNAs in the two groups are differently localized in cell compartments, we deep-sequenced RNA from cytoplasmic and nuclear compartments during early developmental stages. The analysis of these compartment specific datasets revealed group-1 lncRNAs are cytosolic. Based on the cytosolic nature of group-1 RNAs and their higher complementarity to the overlapping developmental mRNAs, we speculate that the group-1 RNAs might function similar to microRNAs in silencing spurious expression of developmental genes. Group-1 and group-2 RNAs are also distinct in terms of their genomic configuration, conservation, length and transcriptional regulation. These results are not only important in understanding the role of antisense RNAs in development but also for predicting the nature of association between antisense lncRNA and overlapping protein-coding genes.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Pillay, S., Takahashi, H., Carninci, P., Kanhere, A.. 2020-02-09. Antisense ncRNAs during early vertebrate development are divided in groups with distinct features. https://doi.org/10.1101/2020.02.08.940148

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

SPACE-Tag Enables High-Throughput Spatial Chromatin Profiling With CUT&Tag

Spatial epigenomics maps chromatin states within intact tissues, yet current methods remain limited by accessibility and scale. We developed SPACE-Tag, a spatial CUT&Tag framework that converts epigenetic marks-associated DNA into polyadenylated RNA through T7 based linear amplification, enabling direct integration with standard spatial transcriptomic workflows. Applied to the mouse brain, SPACETag resolved activating and repressive chromatin landscapes, recovered region-specific gene regulatory programs across anatomical domains, and showed strong correlation with existing bulk and single cell reference data. We generated an integrated multimodal atlas of the aging mouse brain, profiling five histone modifications and the transcriptome in parallel across the adult lifespan to establish the largest spatial multimodal dataset to date. This analysis uncovered sharp regional divergence with aging in the brain: fiber tracts showed widespread transcriptional downregulation, often without nearby chromatin state transitions, whereas the isocortex showed coordinated chromatin transcriptome changes, including an H3K4me1 peak module that increased with age, was enriched at super-enhancers and linked to upregulation of neuronal plasticity regulators. These findings highlight the power of multimodal and high throughput spatial genomics in uncovering the divergent regulatory logic that governs tissue-specific vulnerability and resilience in the aging brain.

genomics↗

Long-read DNA sequencing reveals global hypomethylation and focal hypermethylation in SDHx-deficient pheochromocytoma and paraganglioma

Pheochromocytomas and paragangliomas (PPGL) are highly heritable neuroendocrine tumors of the autonomic ganglia. Genomic DNA in most cancer cells is hypomethylated. However, DNA in PPGLs secondary to mutations in succinate dehydrogenase complex (SDHx) genes is reportedly hypermethylated due to succinate-mediated inhibition of DNA demethylases. We used nanopore long-read sequencing to characterize the methylome of tumor and white blood cell DNA from SDHx and non-SDHx PPGL patients, alongside normal adrenal medulla. We find that both SDHx and non-SDHx PPGLs are globally hypomethylated, particularly at centromeres. In normal adrenal medulla, CpG islands marked by H3K4 methylation are hypomethylated, whereas CpG islands lacking H3K4 methylation are hypermethylated. In SDHx-related PPGL, some H3K4me-marked CpG islands are hypermethylated, but most are not. We propose that DNA methylation in SDHx-related PPGL reflects the global hypomethylation generally observed in tumors, partly offset by succinate-mediated inhibition of TET DNA demethylases. Opposing effects of succinate may alter the balance between DNA methylation (indirect inhibition of the DNMT3A/B DNA methylases via inhibition of H3K4me demethylases) and DNA demethylation (inhibition of TET DNA demethylases) at active CpG islands.

genomics↗

High piRNA abundance is a hallmark of evolutionarily persistent piRNA-producing loci.

PIWI-interacting RNAs (piRNAs) silence transposons in the germline, and the loci that produce them diverge rapidly between species. Yet, some loci retain both their genomic location and their piRNA production across large evolutionary distances, and the basis for this conservation is unclear. To identify the features that distinguish these persistent loci, we compared piRNA production at orthologous loci in three closely related mouse species, contrasting loci that produce piRNAs in all three species with those that do so in only one. Transposon content and UTR features, often linked to piRNA production, did not distinguish the two groups. Transcription extending beyond gene ends (readthrough) was more frequent at conserved loci, but did not explain conservation once the amount of piRNAs produced was taken into account. Instead, we found that the conserved loci are those that produce the most piRNAs. The same association holds true in human and two other primate species. We speculate that most piRNAs expressed in testis are tolerated molecular noise, and that only the highly expressed minority are likely to be functional.

genomics↗