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Sen R.,Gyanxet | Ghosal S.,Indian Association for The Cultivation of Science | Das S.,Indian Association for The Cultivation of Science | Balti S.,Indian Association for The Cultivation of Science | And 2 more authors.
The Scientific World Journal | Year: 2014

Competing endogenous RNA, ceRNA, vie with messenger RNAs (mRNAs) for microRNAs (miRNAs) with shared miRNAs responses elements (MREs) and act as modulator of miRNA by influencing the available level of miRNA. It has recently been discovered that, apart from protein-coding ceRNAs, pseudogenes, long noncoding RNAs (lncRNAs), and circular RNAs act as miRNA "sponges" by sharing common MRE, inhibiting normal miRNA targeting activity on mRNA. These MRE sharing elements form the posttranscriptional ceRNA network to regulate mRNA expression. ceRNAs are widely implicated in many biological processes. Recent studies have identified ceRNAs associated with a number of diseases including cancer. This brief review focuses on the molecular mechanism of ceRNA as part of the complex post-transcriptional regulatory circuit in cell and the impact of ceRNAs in development and disease. © 2014 Rituparno Sen et al.


Das S.,Indian Association for The Cultivation of Science | Mitra S.,Gyanxet | Chakrabarti J.,Indian Association for The Cultivation of Science
Journal of Biomolecular Structure and Dynamics | Year: 2010

Some coding (mRNA) genes are known to express into several different amino-acid chains by intron and exon shuffling. There are computational arguments that an analogous mechanism may give rise to two different products from a single non-coding gene. We propose, based on bioinformatics' evidence, that the number of different products from some of these non-coding genes may indeed be greater than two. The present study demonstrates that, in some cases, intron repositioning and partial exon-intron shuffling lead to newer putative tRNAs. An intricate and entangled organizational network performs a complex optimization of the secondary structures at the exon-intron boundaries. We find up to four different RNAs are encoded cryptically in a single composite tRNA gene. But it is the remarkably high fidelity of the secondary structures and the conserved sequences of all the tRNAs that are embedded that leads to this hypothesis. ©Adenine Press (2010).


Ghosal S.,Indian Association for The Cultivation of Science | Das S.,Indian Association for The Cultivation of Science | Sen R.,Gyanxet | Chakrabarti J.,Indian Association for The Cultivation of Science
Frontiers in Genetics | Year: 2014

Host-virus interaction via host cellular components has been an important field of research in recent times. RNA interference mediated by short interfering RNAs and microRNAs (miRNA), is a widespread anti-viral defense strategy. Importantly, viruses also encode their own miRNAs. In recent times miRNAs were identified as key players in host-virus interaction. Furthermore, viruses were shown to exploit the host miRNA networks to suite their own need. The complex cross-talk between host and viral miRNAs and their cellular and viral targets forms the environment for viral pathogenesis. Apart from protein-coding mRNAs, non-coding RNAs may also be targeted by host or viral miRNAs in virus infected cells, and viruses can exploit the host miRNA mediated gene regulatory network via the competing endogenous RNA effect. A recent report showed that viral U-rich non-coding RNAs called HSUR, expressed in primate virus herpesvirus saimiri (HVS) infected T cells, were able to bind to three host miRNAs, causing significant alteration in cellular level for one of the miRNAs. We have predicted protein coding and non protein-coding targets for viral and human miRNAs in virus infected cells. We identified viral miRNA targets within host non-coding RNA loci from AGO interacting regions in three different virus infected cells. Gene ontology (GO) and pathway enrichment analysis of the genes comprising the ceRNA networks in the virus infected cells revealed enrichment of key cellular signaling pathways related to cell fate decisions and gene transcription, like Notch and Wnt signaling pathways, as well as pathways related to viral entry, replication and virulence. We identified a vast number of non-coding transcripts playing as potential ceRNAs to the immune response associated genes; e.g., APOBEC family genes, in some virus infected cells. All these information are compiled in HumanViCe (http://gyanxet-beta.com/humanvice), a comprehensive database that provides the potential ceRNA networks in virus infected human cells. © 2014 Ghosal, Das, Sen and Chakrabarti.


Ghosal S.,Indian Association for The Cultivation of Science | Das S.,Indian Association for The Cultivation of Science | Sen R.,Gyanxet | Basak P.,Jadavpur University | Chakrabarti J.,Indian Association for The Cultivation of Science
Frontiers in Genetics | Year: 2013

Circular RNAs are new players in regulation of post transcriptional gene expression. Animal genomes express many circular RNAs from diverse genomic locations. A recent study has validated a fairly large number of circular RNAs in human, mouse, and nematode. Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Their interaction with disease associated miRNAs indicates that circular RNAs are important for disease regulation. In this paper we studied the potential association of circular RNAs (circRNA) with human diseases in two different ways. Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated. For the miRNAs associated with individual diseases, we constructed a network of predicted interactions between the miRNAs and protein coding, long non-coding and circular RNA genes. We carried out gene ontology (GO) enrichment analysis on the set of protein coding genes in the miRNA- circRNA interactome of individual diseases to check the enrichment of genes associated with particular biological processes. Secondly, disease associated SNPs were mapped on circRNA loci, and Argonaute (Ago) interaction sites on circular RNAs were identified. We compiled a database of disease-circRNA association in Circ2Traits (http://gyanxet-beta.com/circdb/), the first comprehensive knowledgebase of potential association of circular RNAs with diseases in human. © 2013 Ghosal, Das, Sen, Basak and Chakrabarti.


Das S.,Indian Association for The Cultivation of Science | Ghosal S.,Indian Association for The Cultivation of Science | Sen R.,Gyanxet | Chakrabarti J.,Indian Association for The Cultivation of Science
PLoS ONE | Year: 2014

Long noncoding RNA (lncRNA) influences post-transcriptional regulation by interfering with the microRNA (miRNA) pathways, acting as competing endogenous RNA (ceRNA). These lncRNAs have miRNA responsive elements (MRE) in them, and control endogenous miRNAs available for binding with their target mRNAs, thus reducing the repression of these mRNAs. ln CeDB provides a database of human lncRNAs (from GENCODE 19 version) that can potentially act as ceRNAs. The putative mRNA targets of human miRNAs and the targets mapped to AGO clipped regions are collected from TargetScan and StarBase respectively. The lncRNA targets of human miRNAs (up to GENCODE 11) are downloaded from miRCode database. miRNA targets on the rest of the GENCODE 19 lncRNAs are predicted by our algorithm for finding seed-matched target sites. These putative miRNA-lncRNA interactions are mapped to the Ago interacting regions within lncRNAs. To find out the likelihood of an lncRNA-mRNA pair for actually being ceRNA we take recourse to two methods. First, a ceRNA score is calculated from the ratio of the number of shared MREs between the pair with the total number of MREs of the individual candidate gene. Second, the P-value for each ceRNA pair is determined by hypergeometric test using the number of shared miRNAs between the ceRNA pair against the number of miRNAs interacting with the individual RNAs. Typically, in a pair of RNAs being targeted by common miRNA(s), there should be a correlation of expression so that the increase in level of one ceRNA results in the increased level of the other ceRNA. Near-equimolar concentration of the competing RNAs is associated with more profound ceRNA effect. In lnCeDB one can not only browse for lncRNA-mRNA pairs having common targeting miRNAs, but also compare the expression of the pair in 22 human tissues to estimate the chances of the pair for actually being ceRNAs. Availability: Downloadable freely from http://gyanxet-beta.com/lncedb/. © 2014 Das et al.


PubMed | Indian Association for The Cultivation of Science and Gyanxet
Type: | Journal: Scientific reports | Year: 2016

Some earlier studies have reported an alternative mode of microRNA-target interaction. We detected target regions within mRNA transcripts from AGO PAR-CLIP that did not contain any conventional microRNA seed pairing but only had non-conventional binding sites with microRNA 3 end. Our study from 7 set of data that measured global protein fold change after microRNA transfection pointed towards the association of target protein fold change with 6-mer and 7-mer target sites involving microRNA 3 end. We developed a model to predict the degree of microRNA target regulation in terms of protein fold changes from the number of different conventional and non-conventional target sites present in the target, and found significant correlation of its output with protein expression changes. We validated the effect of non-conventional interactions with target by modulating the abundance of microRNA in a human breast cancer cell line MCF-7. The validation was done using luciferase assay and immunoblot analysis for our predicted non-conventional microRNA-target pair WNT1 (3 UTR) and miR-367-5p and immunoblot analysis for another predicted non-conventional microRNA-target pair MYH10 (coding region) and miR-181a-5p. Both experiments showed inhibition of targets by transfection of microRNA mimics that were predicted to have only non-conventional sites.


PubMed | Indian Association for The Cultivation of Science and Gyanxet
Type: Journal Article | Journal: PloS one | Year: 2014

Long noncoding RNA (lncRNA) influences post-transcriptional regulation by interfering with the microRNA (miRNA) pathways, acting as competing endogenous RNA (ceRNA). These lncRNAs have miRNA responsive elements (MRE) in them, and control endogenous miRNAs available for binding with their target mRNAs, thus reducing the repression of these mRNAs. lnCeDB provides a database of human lncRNAs (from GENCODE 19 version) that can potentially act as ceRNAs. The putative mRNA targets of human miRNAs and the targets mapped to AGO clipped regions are collected from TargetScan and StarBase respectively. The lncRNA targets of human miRNAs (up to GENCODE 11) are downloaded from miRCode database. miRNA targets on the rest of the GENCODE 19 lncRNAs are predicted by our algorithm for finding seed-matched target sites. These putative miRNA-lncRNA interactions are mapped to the Ago interacting regions within lncRNAs. To find out the likelihood of an lncRNA-mRNA pair for actually being ceRNA we take recourse to two methods. First, a ceRNA score is calculated from the ratio of the number of shared MREs between the pair with the total number of MREs of the individual candidate gene. Second, the P-value for each ceRNA pair is determined by hypergeometric test using the number of shared miRNAs between the ceRNA pair against the number of miRNAs interacting with the individual RNAs. Typically, in a pair of RNAs being targeted by common miRNA(s), there should be a correlation of expression so that the increase in level of one ceRNA results in the increased level of the other ceRNA. Near-equimolar concentration of the competing RNAs is associated with more profound ceRNA effect. In lnCeDB one can not only browse for lncRNA-mRNA pairs having common targeting miRNAs, but also compare the expression of the pair in 22 human tissues to estimate the chances of the pair for actually being ceRNAs.Downloadable freely from http://gyanxet-beta.com/lncedb/.

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