Human Long Intergenic Noncoding RNA Linc-ADAL Knockdown in Mature Adipocytes using Lentiviral ShRNA
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE95173 | GEO | 2019/02/13
REPOSITORIES: GEO
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Project description:Long intergenic non-coding RNAs (lincRNAs) are transcripts longer than 200 nucleotides that are transcribed from non-coding loci yet undergo biosynthesis similar to coding mRNAs. The disproportional number of lincRNAs expressed in testes suggests that lincRNAs are important during gametogenesis, but experimental evidence has implicated very few lincRNAs in this process. We took advantage of the relatively limited number of lincRNAs in the genome of the nematode Caenorhabditis elegans to systematically analyse the functions of lincRNAs during meiosis. We deleted six lincRNA genes that are highly and dynamically expressed in the C. elegans gonad and tested the effects on central meiotic processes. Surprisingly, whereas the lincRNA deletions did not strongly impact fertility, germline apoptosis, crossovers, or synapsis, linc-4 was required for somatic growth. Slower growth was observed in linc-4-deletion mutants and in worms depleted of linc-4 using RNAi, indicating that linc-4 transcripts are required for this post-embryonic process. Unexpectedly, analysis of worms depleted of linc-4 in soma versus germline showed that the somatic role stems from linc-4 expression in germline cells. This unique feature suggests that some lincRNAs, like some small non-coding RNAs, are required for germ-soma interactions
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Project description:Little is known how lincRNAs are involved in skeletal myogenesis. Here we describe the discovery of a novel lincRNA, Linc-YY1 from the promoter of transcription factor (TF) Yin Yang 1 (YY1) gene. We demonstrate that Linc-YY1 is dynamically regulated during myogenesis in vitro and in vivo. Gain or loss of function of Linc-YY1 in C2C12 myoblast cells or satellite cells alters myogenic differentiation and in injured muscles impacts the course of regeneration. Further studies suggest LincYY1 may interact with YY1 through its middle domain to evict YY1
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Project description:Adipose tissue remodeling and dysfunction, characterized by increased inflammation and insulin resistance, play a central role in obesity-related development of type 2 diabetes (T2DM) and cardiovascular diseases. Long intergenic non-coding RNAs (lincRNAs) are important regulators of cellular functions. Here we describe the functions of linc-ADAIN (ADipose Anti-INflammatory), an adipose lincRNA that is downregulated in white adipose tissue of obese humans. We demonstrate that linc-ADAIN knockdown (KD) increases KLF5 and IL-8 mRNA stability and translation, by interacting with IGF2BP2. Upregulation of KLF5 and IL-8, via linc-ADAIN KD, led to an enhanced adipogenic program and adipose tissue inflammation, mirroring the obese state, in vitro and in vivo, KD of linc-ADAIN in human ASC hTERT adipocytes implanted into mice, increased adipocyte size and macrophage infiltration compared to implanted control adipocytes, mimicking hallmark features of obesity-induced adipose tissue remodeling. Linc-ADAIN is an anti-inflammatory lincRNA that limits adipose tissue expansion and lipid storage.
2024-04-16 | GSE263852 | GEO
Project description:It has become clear that long intergenic noncoding RNAs (lincRNAs) are an important layer of genome regulation. Thousands have been identified in mammals, yet only a few have been tested through genetic ablation in animal models. Of the few that have, many yields weak to unobservable phenotypes, raising the question of their in vivo relevance. To more broadly investigate the functional relevance of lincRNAs in physiological conditions, we developed a collection of 18 lincRNA knockout strains. We found that two knockout strains, linc-Sox2 and linc-Foxf1a (Fendrr), exhibit perinatal lethal phenotypes in addition to multiple developmental abnormalities. Notably, in depth analysis of a third mutant strain, linc-Brn1b-/-, revealed defects in brain development, with distinct abnormalities in class-specific generation of upper layer II/III-IV neurons in the neocortex. Thus far, we found at least 6 of 18 mutant strains exhibit distinct developmental or lethality phenotypes. Therefore, this study demonstrates that lincRNAs are required for life and play critical roles during mammalian development, highlighting the importance of studying them further to better understand the molecular mechanisms leading to disease. Minimum 2 replicates each of select wild type and lincRNA knockout embryonic and postnatal tissues for three distinct lincRNA knockout mouse strains.
2013-11-30 | E-GEOD-49581 | biostudies-arrayexpress
Project description:Long intergenic noncoding RNAs (lincRNA) transcribed from intergenic regions of eukaryotic genomes play important roles in key biological processes; yet, plant lincRNAs remain poorly characterized. Here we profiled lincRNA expression in inflorescences, leaves and roots using ATH lincRNA v1 array. we found 92% lincRNAs could be detected in at least 2 ATH lincRNA v1 arrays and majority of the lincRNAs were expressed at levels higher than those of pri-miRNAs but lower than those of mRNAs.Using a cut-off of 2-fold change, we identified 149 lincRNAs preferentially expressed in inflorescences, 232 in leaves and 164 in roots.
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Project description:Long intergenic noncoding RNAs (lincRNA) transcribed from intergenic regions of eukaryotic genomes play important roles in key biological processes; yet, plant lincRNAs remain poorly characterized. Here we profiled lincRNA expression in inflorescences, leaves and roots using ATH lincRNA v1 array. we found 92% lincRNAs could be detected in at least 2 ATH lincRNA v1 arrays and majority of the lincRNAs were expressed at levels higher than those of pri-miRNAs but lower than those of mRNAs.Using a cut-off of 2-fold change, we identified 149 lincRNAs preferentially expressed in inflorescences, 232 in leaves and 164 in roots. Nine arrays were hybridized with RNAs from inflorescences, leaves and roots with 3 biological replicates.
2011-08-05 | E-GEOD-30394 | biostudies-arrayexpress
Project description:Long intergenic noncoding RNAs (lincRNAs) transcribed from intergenic regions play important roles in key biological processes.Analysis of published transcriptom datasets suggested some lincRNAs may be regulated by SERRATE,CBP20 and CBP80 in Arabidopsis. To further investigate the regulation, we use Arabidopsis lincRNA arrays v1 to detect lincRNA expression in se-2 and cbp20/80 double mutants.We found the expression levels of 940 lincRNAs (20%) out of the 4,634 lincRNAs with probes in array were significantly alerted in all mutants (P-value of eBays ANOVA < 0.05 & fold change of signal intensity > 2). This group included 525 up-regulated and 415 down-regulated lincRNAs.
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Project description:Through deep RNA-seq in human subcutaneous adipose bioposies and established long noncoding RNAs (lincRNAs) annotations, we identified human lincRNAs expressed in all subjects, including subsets of lincRNAs that exhibit differential expression by sex and race. Our comprehensive profiling on subcutaneous adipose lincRNA transcriptome provides great resource to advance novel understanding of genetic regulation in adipose biology.
2017-08-30 | GSE76404 | GEO
Project description:Long intergenic noncoding RNAs (lincRNAs) transcribed from intergenic regions play important roles in key biological processes.Analysis of published transcriptom datasets suggested some lincRNAs may be regulated by SERRATE,CBP20 and CBP80 in Arabidopsis. To further investigate the regulation, we use Arabidopsis lincRNA arrays v1 to detect lincRNA expression in se-2 and cbp20/80 double mutants.We found the expression levels of 940 lincRNAs (20%) out of the 4,634 lincRNAs with probes in array were significantly alerted in all mutants (P-value of eBays ANOVA < 0.05 & fold change of signal intensity > 2). This group included 525 up-regulated and 415 down-regulated lincRNAs. Seedlings(Col-0), Seedlings(se-2), Seedlings(cbp20,80 double mutant) x 3 biological replicates
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Project description:Thousands of long intergenic non-coding RNAs (lincRNAs) are transcribed throughout the vertebrate genome. A subset of lincRNAs enriched in developing brains have recently been found to contain cryptic open reading frames and are speculated to encode micropeptides. However, systematic identification and functional assessment of these transcripts have been hindered by technical challenges caused by their small size. Here we show that two putative lincRNAs (linc-mipep, also called lnc-rps25, and linc-wrb) encode micropeptides with homology to the vertebrate-specific chromatin architectural protein, Hmgn1, and demonstrate that they are required for development of vertebrate-specific brain cell types. Specifically, we show that NMDA receptor-mediated pathways are dysregulated in zebrafish lacking these micropeptides and that their loss preferentially alters the gene regulatory networks that establish cerebellar cells and oligodendrocytes - evolutionarily newer cell types that develop postnatally in humans. These findings reveal a key missing link in the evolution of vertebrate brain cell development and illustrate a genetic basis for how some neural cell types are more susceptible to chromatin disruptions, with implications for neurodevelopmental disorders and disease.
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