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The knowledge of what separates us genetically from our less-evolved relatives is crucial for gaining new biomedical insights about the human-chimpanzee relatedness for the use of appropriate stand-in towards the development of new treatments and diagnostic aids for various ailments. Although the genomes of humans and chimpanzees share 99% similarity, significant differences exist between the two species in their non-coding intronic regions. However, no work has been carried out in the aspects of target prediction concerning the ‘predicted homology’ in their microRNA sequences. Non-coding miRNAs which are post-transcriptional regulators of development, differentiation, growth, and metabolism, harboring the intronic regions may be crucial for expanding the horizons of our understanding. In this study, we proposed to perform the target prediction for the human-chimp miRNA homologs in the PHEX gene of the human X chromosome using various computational tools and databases. We identified a total of 1296 human miRNAs, 46, 957 gene targets, and 30, 563 targets of human and homologous chimp miRNAs respectively. Furthermore, we analysed gene interacting networks to identify the top interacting targets in both the species. Finally, we interpreted the biological importance of top-interacting miRNAs and their targets. The results demonstrated varying levels of multiplicity and cooperativity between the predicted miRNAs and target genes in the two genera. Such miRNAs may be responsible for the dysregulation of gene expression in several signaling pathways.

Intronic miRNAs, residing in intronic regions of host genes, are thought to be co-transcribed from their host genes and present consistent expression patterns with host genes. Recent studies reported a few intronic miRNAs with discordant expression with their host genes. We therefore aimed to understand the expression pattern of intronic miRNAs and their host genes in hepatocellular carcinoma (HCC) and reveal possible associated molecular mechanisms. Our genome wide integration analysis of miRNA and mRNA transcriptomes, in three dataset from 550 patients with HCC, found that a large amount of miRNA-host gene pairs were discordantly expressed. Consistent results were also revealed in 775 breast cancer patients. Further, most of HCC-related intronic miRNAs were predicted to have distinct upstream regulators and independent proximal promoter signals from host genes. The discordant expression of representative pairs, miR-26s/CTDSPs, was validated experimentally. We have also identified the independent transcriptional start site, promoter signal, and transcriptional factor of miR-26b from its host gene. Collectively, discordant expression of intronic miRNAs and their host genes was relatively ubiquitous and the intronic miRNA "independent transcription" may partially contribute to such a phenotype.

Development of sequencing techniques allowed us to determine genomic sequences in many organisms. Such a determined genome consists of not only protein-coding genes but also noncoding RNA (ncRNA) genes. We should analyze evolutional histories of such genes to estimate evolutional directions in future. Meanwhile, recent studies showed that some ncRNA genes are located in intragenic regions in protein-coding genes, which are called host genes. We considered that such information can help us to discuss gene evolutions. In this study, we constructed a database to analyze evolutions of protein-coding and noncoding genes based on gene locations in genomic sequences. We found that 547 out of 2,691 human host genes are orthologous to 546 out of 1,633 mouse host genes. Such orthologous host genes are involved in similar biological functions but some non-orthologous host genes have different functions. For example, non-orthologous host genes in human are annotated as neuron-related terms but such genes in mouse are not. Meanwhile, similarity searches for intronic microRNA (miRNA) genes between human and mouse showed that 85 out of the orthologous host genes have retained miRNA genes in the intronic regions. 64 out of such genes have retained intronic miRNA genes among human, mouse and rat. These results suggest that some orthologous genes have retained ncRNA genes in the intronic regions in the evolutionary process.

The molecular pathogenesis underlying the primary myelofibrosis (PMF) progression to acute myeloid leukemia (AML) is still not well defined. The involvement of microRNA (miRNA) is actually helping to shed light on an important issue in the occurrence of myeloproliferative neoplasms (MPNs). However, the role of intronic miRNA, derived from the intron regions of gene transcripts, has never been reported in MPNs. In this study, we describe a PMF case evolved to AML with a t(12;18)(p13;q12) rearrangement showing the downregulation of the intronic miR_4319 and the overexpression of its host gene, SET binding protein (SETBP1). A possible molecular mechanism regulating the PMF progression to AML is discussed.

UNLABELLED IntmiR is a manually curated database of published intronic miRNAs of Human and Mouse genome. Each entry in the database, aims at providing a complete resource of intronic miRNA with their target gene and deregulation in various diseases with related tissues and pathways. The current release contains 426 intronic miRNA loci from human and 76 from mouse, expressing distinct target mRNA sequences. Database gives information on an intronic miRNA-disease relationship, including miRNA ID, pathaway connected and related tissues. All entries can be retrieved by miRNA ID or target gene. IntmiR is freely available at rgcb.res.in/intmir. AVAILABILITY The database is available for free at rgcb.res.in/intmir.

We introduce a molecular toolbox for manipulation of neuronal gene expression in vivo. The toolbox includes promoters, ion channels, optogenetic tools, fluorescent proteins, and intronic artificial microRNAs. The components are easily assembled into adeno-associated virus (AAV) or lentivirus vectors using recombination cloning. We demonstrate assembly of toolbox components into lentivirus and AAV vectors and use these vectors for in vivo expression of inwardly rectifying potassium channels (Kir2.1, Kir3.1, and Kir3.2) and an artificial microRNA targeted against the ion channel HCN1 (HCN1 miRNA). We show that AAV assembled to express HCN1 miRNA produces efficacious and specific in vivo knockdown of HCN1 channels. Comparison of in vivo viral transduction using HCN1 miRNA with mice containing a germ line deletion of HCN1 reveals similar physiological phenotypes in cerebellar Purkinje cells. The easy assembly and re-usability of the toolbox components, together with the ability to up- or down-regulate neuronal gene expression in vivo ,m ay be useful for applications in many areas of neuroscience.

The importance of microRNA (miRNA) in modulating gene expression at the post-transcriptional level is well known. Such regulation has been shown to influence the dynamics of several regulatory networks including the cell cycle. In this study we incorporated regulatory effects of intronic miRNA into an existing mathematical model of the cell cycle through the use of an existing ‘proxy’ protein – the host protein. It was observed that the incorporation of intronic miRNA mediated regulation improved the performance of the model resulting in a closer match to experimental results. To test the universality of this approach we compared the effects of intronic miRNA mediated regulation and host protein mediated regulation. Further, we compared miRNA mediated and protein mediated positive and negative feedback regulations of the target protein. We found that the target protein profiles were predominantly similar. These observations show the applicability of our method for incorporating intronic miRNA mediated dynamic effects in models for regulation of gene expression.