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The tissue specific regulation of miR22 expression in the lung and brain by ribosomal protein L29.

ABSTRACT: Endogenous miR22 is associated with a diverse range of biological processes through post-translational modification of gene expression and its deregulation results in various diseases including cancer. Its expression is usually tissue or cell-specific, however, the reasons behind this tissue or cell specificity are not clearly outlined till-date. Therefore, our keen interest was to investigate the mechanisms of tissue or cell-specific expression of miR22. In the current study, miR22 expression showed a tissues-specific difference in the poly(I:C) induced inflammatory mouse lung and brain tissues. The cell-specific different expression of miR22 was also observed in inflammatory glial cells and endothelial cells. The pattern of RPL29 expression was also similar to miR22 in these tissues and cells under the same treatment. Interestingly, the knockdown of RPL29 exerted an inhibitory effect on miR22 and its known transcription factors including Fos-B and c-Fos. Fos-B and c-Fos were also differentially expressed in the two cell lines transfected with poly(I:C). The knockdown of c-Fos also exerted its negative effects on miR22 expression in both cells. These findings suggest that RPL29 might have regulatory roles on tissue or cell-specific expression of miR22 through the transcription activities of c-Fos and also possibly through Fos-B.

SUBMITTER: Ali MI

PROVIDER: S-EPMC7530758 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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The tissue specific regulation of miR22 expression in the lung and brain by ribosomal protein L29.

Ali Mohammad Ishaque MI Li Linrui L Li Lexing L Yao Lun L Liu Jie J Gu Wei W Huang Shuguang S Wang Bingyu B Liu Guoquan G

Scientific reports 20201001 1

Endogenous miR22 is associated with a diverse range of biological processes through post-translational modification of gene expression and its deregulation results in various diseases including cancer. Its expression is usually tissue or cell-specific, however, the reasons behind this tissue or cell specificity are not clearly outlined till-date. Therefore, our keen interest was to investigate the mechanisms of tissue or cell-specific expression of miR22. In the current study, miR22 expression s ...[more]

PMID: 33004906

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Project description:Genes implicated in schizophrenia are enriched in networks differentially regulated during human CNS development. Neuregulin 3 (NRG3), a brain-enriched neurotrophin, undergoes alternative splicing and is implicated in several neurological disorders with developmental origins. Isoform-specific increases in NRG3 are observed in schizophrenia and associated with rs10748842, a NRG3 risk polymorphism, suggesting NRG3 transcriptional dysregulation as a molecular mechanism of risk. The authors quantitatively mapped the temporal trajectories of NRG3 isoforms (classes I-IV) in the neocortex throughout the human lifespan, examined whether tissue-specific regulation of NRG3 occurs in humans, and determined if abnormalities in NRG3 transcriptomics occur in mood disorders and are genetically determined.NRG3 isoform classes I-IV were quantified using quantitative real-time polymerase chain reaction in human postmortem dorsolateral prefrontal cortex from 286 nonpsychiatric control individuals, from gestational week 14 to 85 years old, and individuals diagnosed with either bipolar disorder (N=34) or major depressive disorder (N=69). Tissue-specific mapping was investigated in several human tissues. rs10748842 was genotyped in individuals with mood disorders, and association with NRG3 isoform expression examined.NRG3 classes displayed individually specific expression trajectories across human neocortical development and aging; classes I, II, and IV were significantly associated with developmental stage. NRG3 class I was increased in bipolar and major depressive disorder, consistent with observations in schizophrenia. NRG3 class II was increased in bipolar disorder, and class III was increased in major depression. The rs10748842 risk genotype predicted elevated class II and III expression, consistent with previous reports in the brain, with tissue-specific analyses suggesting that classes II and III are brain-specific isoforms of NRG3.Mapping the temporal expression of genes during human brain development provides vital insight into gene function and identifies critical sensitive periods whereby genetic factors may influence risk for psychiatric disease. Here the authors provide comprehensive insight into the transcriptional landscape of the psychiatric risk gene, NRG3, in human neocortical development and expand on previous findings in schizophrenia to identify increased expression of developmentally and genetically regulated isoforms in the brain of patients with mood disorders. Principally, the finding that NRG3 classes II and III are brain-specific isoforms predicted by rs10748842 risk genotype and are increased in mood disorders further implicates a molecular mechanism of psychiatric risk at the NRG3 locus and identifies a potential developmental role for NRG3 in bipolar disorder and major depression. These observations encourage investigation of the neurobiology of NRG3 isoforms and highlight inhibition of NRG3 signaling as a potential target for psychiatric treatment development.

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The tissue specific regulation of miR22 expression in the lung and brain by ribosomal protein L29.

Publications

The tissue specific regulation of miR22 expression in the lung and brain by ribosomal protein L29.

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