scholarly journals Transcriptional Gene Silencing of the Autism-Associated Long Noncoding RNA MSNP1AS in Human Neural Progenitor Cells

2016 ◽  
Vol 38 (5) ◽  
pp. 375-383 ◽  
Author(s):  
Jessica J. DeWitt ◽  
Patrick M. Hecht ◽  
Nicole Grepo ◽  
Brent Wilkinson ◽  
Oleg V. Evgrafov ◽  
...  
Keyword(s):  
Immune Response ◽  
Chromatin Remodeling ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Multiple Comparisons ◽  
Neural Progenitor ◽  
Autism Spectrum ◽  
Biological Processes ◽  
Altered Expression ◽  
Genome Wide

The long noncoding RNA MSNP1AS (moesin pseudogene 1, antisense) is a functional element that was previously associated with autism spectrum disorder (ASD) with genome-wide significance. Expression of MSNP1AS was increased 12-fold in the cerebral cortex of individuals with ASD and 22-fold in individuals with a genome-wide significantly associated ASD genetic marker on chromosome 5p14.1. Overexpression of MSNP1AS in human neuronal cells caused decreased expression of moesin protein, which is involved in neuronal process stability. In this study, we hypothesize that MSNP1AS knockdown impacts global transcriptome levels. We transfected the human neural progenitor cell line SK- N-SH with constructs that caused a 50% suppression of MSNP1AS expression. After 24 h, cells were harvested for total RNA isolation. Strand-specific RNA sequencing analysis indicated altered expression of 1,352 genes, including altered expression of 318 genes following correction for multiple comparisons. Expression of the OAS2 gene was increased >150-fold, a result that was validated by quantitative PCR. Gene ontology analysis of the 318 genes with altered expression following correction for multiple comparisons indicated that upregulated genes were significantly enriched for genes involved in immune response, and downregulated genes were significantly enriched for genes involved in chromatin remodeling. These data indicate multiple transcriptional and translational functions of MSNP1AS that impact ASD-relevant biological processes. Chromatin remodeling and immune response are biological processes implicated by genes with rare mutations associated with ASD. Our data suggest that the functional elements implicated by association of common genetic variants impact the same biological processes, suggesting a possible shared common molecular pathway of ASD.

Abstract P252: Loss of HMGB2 Induces Chromatin Remodeling and Hypertrophic Growth in Cardiomyocytes

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Sarah Franklin ◽  
Haodong Chen ◽  
Scherise Mitchell-Jordan ◽  
Shuxun Ren ◽  
Peipei Ping ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mass Spectrometry ◽  
Chromatin Remodeling ◽  
Nuclear Dna ◽  
Specific Pattern ◽  
Altered Expression ◽  
Hypertrophic Growth ◽  
Knock Down ◽  
Genome Wide ◽  
Chromatin Structural

Nuclear DNA is packaged around the octameric nucleosome core particle, constituting the basic building block of chromatin. Non-nucleosome chromatin structural molecules have been shown to induce higher order packaging of DNA into structurally compact and inactive heterochromatin, or loosely packed and active euchromatin. These chromatin remodeling events are thought to establish a cell type specific pattern of gene expression. During the development of cardiac hypertrophy and failure, genes normally only expressed during development are re-activated. While a number of transcription factors involved in these changes in fetal gene expression have been identified, the means for genome-wide structural remodeling of DNA are unknown. To identify factors controlling genomic plasticity in cardiomyocytes, we used mass spectrometry to quantify chromatin-associated proteins from cardiac nuclei during stages of hypertrophy and failure in the mouse. Adult mice were subjected to cardiac pressure overload by transverse aortic constriction. Chromatin was fractionated from cardiac nuclei and DNA-bound proteins were acid extracted and analyzed by mass spectrometry. We measured chromatin occupancy patterns for >300 proteins during distinct stages of heart failure. To explore the isoform specific roles of individual chromatin structural proteins, we used siRNA to knock-down expression of two high mobility group proteins (HMGB1 and 2) exhibiting altered expression in the hypertrophic heart. Loss of HMGB2 (but not HMGB1) induced robust hypertrophic growth in cardiomyocytes. qRT-PCR analyses demonstrated that HMGB2 is responsible for some but not all changes in the fetal gene program (ANF increased 150% and SERCA decreased 20%, whereas α- and β-MHC were unchanged). To further explore the endogenous regions of the genome under control of HMGB2 packing, we performed microarrays following HMGB2 knockdown. Hypertrophy or HMGB2 knock-down induced global chromatin remodeling conducive to gene expression, as measured by histone post-translational modifications and the ratio of core to linker histones. These studies reveal a novel role of HMGB2 to inhibit hypertrophic growth and provide insights into general principles for genome-wide chromatin remodeling.

scholarly journals Genome-wide analysis of long noncoding RNA and mRNA profiles in PRRSV-infected porcine alveolar macrophages

Genomics ◽  
2020 ◽  
Vol 112 (2) ◽  
pp. 1879-1888
Author(s):  
Junjing Wu ◽  
Xianwen Peng ◽  
Mu Qiao ◽  
Haizhong Zhao ◽  
Mingbo Li ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Genome Wide Analysis ◽  
Genome Wide

scholarly journals Global Long Noncoding RNA and mRNA Expression Changes between Prenatal and Neonatal Lung Tissue in Pigs

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 443 ◽  
Author(s):  
Long Jin ◽  
Silu Hu ◽  
Teng Tu ◽  
Zhiqing Huang ◽  
Qianzi Tang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Lung Tissue ◽  
Long Noncoding Rna ◽  
Lung Development ◽  
Noncoding Rna ◽  
Differentially Expressed ◽  
P Value ◽  
Distal Lung ◽  
Neonatal Lungs

Lung tissue plays an important role in the respiratory system of mammals after birth. Early lung development includes six key stages, of which the saccular stage spans the pre- and neonatal periods and prepares the distal lung for alveolarization and gas-exchange. However, little is known about the changes in gene expression between fetal and neonatal lungs. In this study, we performed transcriptomic analysis of messenger RNA (mRNA) and long noncoding RNA (lncRNA) expressed in the lung tissue of fetal and neonatal piglets. A total of 19,310 lncRNAs and 14,579 mRNAs were identified and substantially expressed. Furthermore, 3248 mRNAs were significantly (FDR-adjusted p value ≤ 0.05, FDR: False Discovery Rate) differentially expressed and were mainly enriched in categories related to cell proliferation, immune response, hypoxia response, and mitochondrial activation. For example, CCNA2, an important gene involved in the cell cycle and DNA replication, was upregulated in neonatal lungs. We also identified 452 significantly (FDR-adjusted p value ≤ 0.05) differentially expressed lncRNAs, which might function in cell proliferation, mitochondrial activation, and immune response, similar to the differentially expressed mRNAs. These results suggest that differentially expressed mRNAs and lncRNAs might co-regulate lung development in early postnatal pigs. Notably, the TU64359 lncRNA might promote distal lung development by up-regulating the heparin-binding epidermal growth factor-like (HB-EGF) expression. Our research provides basic lung development datasets and will accelerate clinical researches of newborn lung diseases with pig models.

scholarly journals An expanded landscape of human long noncoding RNA

2019 ◽  
Vol 47 (15) ◽  
pp. 7842-7856 ◽  
Author(s):  
Shuai Jiang ◽  
Si-Jin Cheng ◽  
Li-Chen Ren ◽  
Qian Wang ◽  
Yu-Jian Kang ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Tumor Metastasis ◽  
Patient Survival ◽  
Clinical Stage ◽  
Biological Processes ◽  
Multiple Sources ◽  
Online Portal ◽  
Tumor Tissues ◽  
User Friendly

Abstract Long noncoding RNAs (lncRNAs) are emerging as key regulators of multiple essential biological processes involved in physiology and pathology. By analyzing the largest compendium of 14,166 samples from normal and tumor tissues, we significantly expand the landscape of human long noncoding RNA with a high-quality atlas: RefLnc (Reference catalog of LncRNA). Powered by comprehensive annotation across multiple sources, RefLnc helps to pinpoint 275 novel intergenic lncRNAs correlated with sex, age or race as well as 369 novel ones associated with patient survival, clinical stage, tumor metastasis or recurrence. Integrated in a user-friendly online portal, the expanded catalog of human lncRNAs provides a valuable resource for investigating lncRNA function in both human biology and cancer development.

Genome-wide analysis of long noncoding RNA signature in human colorectal cancer

Gene ◽  
2015 ◽  
Vol 556 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Yao Xue ◽  
Gaoxiang Ma ◽  
Dongying Gu ◽  
Lingjun Zhu ◽  
Qiuhan Hua ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Human Colorectal Cancer ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Rna Signature

scholarly journals Genome-wide analysis of long noncoding RNA stability

2012 ◽  
Vol 22 (5) ◽  
pp. 885-898 ◽  
Author(s):  
M. B. Clark ◽  
R. L. Johnston ◽  
M. Inostroza-Ponta ◽  
A. H. Fox ◽  
E. Fortini ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Rna Stability ◽  
Genome Wide Analysis ◽  
Genome Wide
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