BackgroundLong noncoding RNAs (lncRNAs) are a recently discovered class of non-protein coding RNAs, which have now increasingly been shown to be involved in a wide variety of biological processes as regulatory molecules. The functional role of many of the members of this class has been an enigma, except a few of them like Malat and HOTAIR. Little is known regarding the regulatory interactions between noncoding RNA classes. Recent reports have suggested that lncRNAs could potentially interact with other classes of non-coding RNAs including microRNAs (miRNAs) and modulate their regulatory role through interactions. We hypothesized that lncRNAs could participate as a layer of regulatory interactions with miRNAs. The availability of genome-scale datasets for Argonaute targets across human transcriptome has prompted us to reconstruct a genome-scale network of interactions between miRNAs and lncRNAs.ResultsWe used well characterized experimental Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) datasets and the recent genome-wide annotations for lncRNAs in public domain to construct a comprehensive transcriptome-wide map of miRNA regulatory elements. Comparative analysis revealed that in addition to targeting protein-coding transcripts, miRNAs could also potentially target lncRNAs, thus participating in a novel layer of regulatory interactions between noncoding RNA classes. Furthermore, we have modeled one example of miRNA-lncRNA interaction using a zebrafish model. We have also found that the miRNA regulatory elements have a positional preference, clustering towards the mid regions and 3′ ends of the long noncoding transcripts. We also further reconstruct a genome-wide map of miRNA interactions with lncRNAs as well as messenger RNAs.ConclusionsThis analysis suggests widespread regulatory interactions between noncoding RNAs classes and suggests a novel functional role for lncRNAs. We also present the first transcriptome scale study on miRNA-lncRNA interactions and the first report of a genome-scale reconstruction of a noncoding RNA regulatory interactome involving lncRNAs.

INTRODUCTION 1.1 EPIGENETIC REGULATION 1.2 CHROMATIN CROSSTALK IN 3D 1.2.1 The innovation of techniques to explore the 3D genome 1.2.2 The genome organizer CTCF and its PARP1 partner 1.2.3 Compartmentalization of nuclear functions in 3D 1.2.4 The active compartments: nuclear interior 1.2.5 The inactive nuclear compartments 1.3 NUCLEOPORINS AND THE GENE GATING PRINCIPLE 1.4 REGULATION OF CIRCADIAN TRANSCRIPTION IN THE COMPARTMENTALIZED NUCLEUS 1.4.1 The central and peripheral clocks 1.4.2 The entrainment of circadian rhythm by external time cues 1.4.3 The clock machinery: driving circadian transcription 1.5 CIRCADIAN CHROMATIN TRANSITIONS 1.5.1 The establishment of active chromatin states by the positive limb 1.5.2 The establishment of repressed chromatin states by the negative limb 1.5.3 Crosstalk between the positive and negative limb of the clock machinery during chromatin transitions 1.6 CIRCADIAN CLOCK, CELLULAR METABOLISM AND COMPLEX DISEASES 2 AIMS 3 METHODS AND MATERIALS 3.1 CELL CULTURES AND TREATMENTS 3.2 RNA/DNA FISH ANALYSES 3.3 IN SITU PROXIMITY LIGATION ASSAY (ISPLA) 3.4 CHROMATIN IN SITU PROXIMITY (CHRISP) 3.5 GRID WIDE-FIELD MICROSCOPY 3.6 CHROMATIN NETWORKS AND INTEGRATION ANALYSES 3.6.1 Circular chromatin conformation capture sequencing (4C-Seq) 3.6.2 Nodewalk 3.7 RNA ANLYSES 3.7.1 Pulse labeling of RNA 3.7.2 The nuclear RNA export assay 3.7.3 mRNA decay analyses 3.7.4 RT-QPCR analysis of transcription 4 RESULTS 4.1 PAPER I: PARP1-AND CTCF-MEDIATED INTERACTIONS BETWEEN ACTIVE AND REPRESSED CHROMATIN AT THE LAMINA PROMOTE OSCILLATING TRANSCRIPTION 4.1.1 Interactome connecting circadian loci and LADs 4.1.2 Molecular ties connecting circadian loci to LADs 4.1.3 The role of the nuclear periphery in circadian transcriptional attenuation 4.1.4 Summary: novel principles in the entrainment of circadian transcription 6 4.2 PAPER II: WNT SIGNALING AND AHCTF1 PROMOTE ONCOGENIC MYC EXPRESSION THROUGH SUPER-ENHANCER-MEDIATED GENE GATING 4.2.1 Regulation of MYC transcription in 3D 4.2.2 Contribution of gene gating to MYC mRNA accumulation 4.2.3 The role of WNT in the super-enhancer mediated gene gating of MYC 5 DISCUSSIONS 5.1 THE ROLE OF NUCLEAR PERIPHERY IN THE REGULATION OF GENE EXPRESSION 5.2 MYC AND THE CIRCADIAN CLOCK 5.3 ADAPTATION TO THE ENVIRONMENT 5.3.1 WNT signaling 5.3.2 Circadian entrainment 5.3.3 Nucleoporins and the transcriptional memory 5.4 CTCF AND PARP1 IN COMPLEX DISEASES 5.4.

This study brings the comprehensive information on epidemiology of SLT use among adults at global level. Ninety percent of SLT burden is in low and low-middle income group of countries and more specifically among the poorest group in such countries. These countries need to have strategies to implement different provisions of the WHO Framework Convention on Tobacco Control. The program in such countries should be targeted towards the poorest communities for effective SLT control.

The advent of high-throughput genome scale technologies has enabled us to unravel a large amount of the previously unknown transcriptionally active regions of the genome. Recent genome-wide studies have provided annotations of a large repertoire of various classes of noncoding transcripts. Long noncoding RNAs (lncRNAs) form a major proportion of these novel annotated noncoding transcripts, and presently known to be involved in a number of functionally distinct biological processes. Over 18 000 transcripts are presently annotated as lncRNA, and encompass previously annotated classes of noncoding transcripts including large intergenic noncoding RNA, antisense RNA and processed pseudogenes. There is a significant gap in the resources providing a stable annotation, cross-referencing and biologically relevant information. lncRNome has been envisioned with the aim of filling this gap by integrating annotations on a wide variety of biologically significant information into a comprehensive knowledgebase. To the best of our knowledge, lncRNome is one of the largest and most comprehensive resources for lncRNAs.Database URL: http://genome.igib.res.in/lncRNome