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Browsing by Subject "microRNAs (miRs)"
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Item The role of Brahma-related gene 1 in regulating the expression of microRNAs in colonic smooth muscle cells(Office of the Vice Chancellor for Research, 2012-04-13) Chen, Meng; Herring, PaulPrevious work by our group has shown that mice harboring null mutation of Brahma-related gene 1 (Brg1)-an ATPase subunit of SWI/SNF (SWItch/Sucrose NonFermentable) chromatin remodeling complex have reduced smooth muscle contractility and disorganized smooth muscle cells (SMCs) in colon, which are similar defects to those of microRNA maturation enzyme Dicer-deficient mice. Recently microRNAs (miRs) such as miR-143/145 have been implicated in the regulation of gene expression essential for smooth muscle cell proliferation and differentiation. Thus we aimed to identify the microRNAs that were involved in regulating the phenotypic changes in Brg1-deficient colonic smooth muscle cells and determine how Brg1 regulated them. The microRNA array screens of colonic smooth muscle and quantitative reverse transcription-polymerase chain reaction assays identified 6 miRs were down-regulated and 6 were up-regulated in smooth muscle specific Brg1 knockout tissue compared with control. Inactivation of endogenous Brg1 by introducing dominant negative Brg1 into wild type SMCs in vitro decreased miR-143/145 expression in smooth muscle cells. In Brg1 null SW13 cells, miR-143/145 were dramatically induced by myogenic transcriptional co-factor myocardin only in the presence of Brg1. Chromatin immunoprecipitation assays demonstrated that myocardin together with Brg1 increased the binding of transcription factor serum response factor (SRF) to the promoter region of miR-143/145 gene cluster. In conclusion, Brg1 together with myocardin can induce the transcription of miR-143/145 through enhancing the binding of SRF to the promoter region in SMCs. Together this suggests that SWI/SNF mediated chromatin remodeling regulates the phenotype of colonic smooth muscle by regulating expression of microRNAs that further modulate expression of their targets.Item SARS-CoV-2 contributes to altering the post-transcriptional regulatory networks across human tissues by sponging RNA binding proteins and micro-RNAs(2020-07-06) Srivastava, Rajneesh; Daulatabad, Swapna Vidhur; Srivastava, Mansi; Janga, Sarath Chandra; BioHealth Informatics, School of Informatics and ComputingThe outbreak of a novel coronavirus SARS-CoV2 responsible for COVID-19 pandemic has caused worldwide public health emergency. Due to the constantly evolving nature of the coronaviruses, SARS-CoV-2 mediated alteration on post-transcriptional gene regulation across human tissues remains elusive. In this study, we systematically dissected the crosstalk and dysregulation of human post-transcriptional regulatory networks governed by RNA binding proteins (RBPs) and micro-RNAs (miRs), due to SARS-CoV-2 infection. We uncovered that 13 out of 29 SARS-CoV- 2 encoded proteins directly interact with 51 human RBPs of which majority of them were abundantly expressed in gonadal tissues and immune cells. We further performed functional analysis of differentially expressed genes in mock treated versus SARS-CoV-2 infected lung cells that revealed an enrichment for immune response, cytokine mediated signaling, and metabolism associated genes. This study also characterized the alternative splicing events in SARS-CoV-2 infected cells compared to control demonstrating that skipped exons and mutually exclusive exons were the most abundant events that potentially contributed to differential outcomes in response to viral infection. Motif enrichment analysis on the RNA genomic sequence of SARS-CoV-2 clearly revealed an enrichment for RBPs such as SRSFs, PCBPs, ELAVs and HNRNPs illustrating the sponging of RBPs by SARS-CoV-2 genome. Similar analysis to study the interactions of miRs with SARS-CoV-2 revealed the potential for several miRs to be sponged, suggesting that these interactions may contribute to altered pos-transcriptional regulation across human tissues. Given the need to understand the interactions of SARS-CoV-2 with key pos-transcriptional regulators in the human genome, this study provides a systematic analysis to dissect the role of dysregulated post-transcriptional regulatory networks controlled by RBPs and miRs, across tissues types during SARS-CoV2 infection.