Kanhere, A. | Search bioRxiv

bioRxiv2020

A long intergenic non-coding RNA regulates nuclear localisation of DNA methyl transferase-1

DNA methyl-transferase-1 or DNMT1 maintains DNA methylation in the genome and is important for regulating gene expression in cells. Aberrant changes in DNMT1 activity are observed in many diseases. Therefore, understanding the mechanisms behind alteration of DNMT1 activity is important. Here, we show that CCDC26, a nuclear long non-coding RNA frequently mutated in myeloid leukaemia, directly interacts with DNMT1. In the absence of CCDC26 RNA, DNMT1 is mis-located in the cytoplasm. As a result, genomic DNA is significantly hypomethylated, which is accompanied by a slower cell growth rate and increased cell death. These results point to a previously unrecognised mechanism of long non-coding RNA mediated subcellular localisation of DNMT1 and regulation of DNA methylation. These observations are significant given the importance of DNMT1 in cancer and number of other diseases.

molecular biology↗

bioRxiv2020

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

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.

genomics↗