Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination

Lima, Diógenes Saulo de; Cardozo, Lucas Esteves; Maracaja-Coutinho, Vinícius; Suhrbier, Andreas; Mane, Karim; Jeffries, David; Silveira, Eduardo Lani Volpe da; Amaral, Paulo; Rappuoli, Rino; Silva, Thushan I. de; Nakaya, Helder I.

doi:10.1073/pnas.1822046116

Cited by 57 publications

(46 citation statements)

References 63 publications

(79 reference statements)

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“…DANCR is notably active in lymphoid organs and T cell differentiation and presents massive increases following influenza vaccination ( 105 , 106 ). Compatible with a regulatory role for DANCR in SARS-CoV-2-generated lung infection, DANCR shares a genomic locus with miR-4449, which is upregulated in airway epithelial cells under respiratory syncytial virus (RSV) infection ( 107 ), and is dysregulated in lymphocytes of multiple myeloma and ankylosing spondylitis patients ( 108 , 109 ).…”

Section: Discussionmentioning

confidence: 99%

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

2020

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The COVID-19 pandemic exerts inflammation-related parasympathetic complications and post-infection manifestations with major inter-individual variability. To seek the corresponding transcriptomic origins for the impact of COVID-19 infection and its aftermath consequences, we sought the relevance of long and short non-coding RNAs (ncRNAs) for susceptibility to COVID-19 infection. We selected inflammation-prone men and women of diverse ages among the cohort of Genome Tissue expression (GTEx) by mining RNA-seq datasets from their lung, and blood tissues, followed by quantitative qRT-PCR, bioinformatics-based network analyses and thorough statistics compared to brain cell culture and infection tests with COVID-19 and H1N1 viruses. In lung tissues from 57 inflammation-prone, but not other GTEx donors, we discovered sharp declines of the lung pathology-associated ncRNA DANCR and the nuclear paraspeckles forming neuroprotective ncRNA NEAT1. Accompanying increases in the acetylcholine-regulating transcripts capable of controlling inflammation co-appeared in SARS-CoV-2 infected but not H1N1 influenza infected lung cells. The lung cells-characteristic DANCR and NEAT1 association with inflammation-controlling transcripts could not be observed in blood cells, weakened with age and presented sex-dependent links in GTEx lung RNA-seq dataset. Supporting active involvement in the inflammatory risks accompanying COVID-19, DANCR’s decline associated with decrease of the COVID-19-related cellular transcript ACE2 and with sex-related increases in coding transcripts potentiating acetylcholine signaling. Furthermore, transcription factors (TFs) in lung, brain and cultured infected cells created networks with the candidate transcripts, indicating tissue-specific expression patterns. Supporting links of post-infection inflammatory and cognitive damages with cholinergic mal-functioning, man and woman-originated cultured cholinergic neurons presented differentiation-related increases of DANCR and NEAT1 targeting microRNAs. Briefly, changes in ncRNAs and TFs from inflammation-prone human lung tissues, SARS-CoV-2-infected lung cells and man and woman-derived differentiated cholinergic neurons reflected the inflammatory pathobiology related to COVID-19. By shifting ncRNA differences into comparative diagnostic and therapeutic profiles, our RNA-sequencing based Resource can identify ncRNA regulating candidates for COVID-19 and its associated immediate and predicted long-term inflammation and neurological complications, and sex-related therapeutics thereof. Our findings encourage diagnostics of involved tissue, and further investigation of NEAT1-inducing statins and anti-cholinergic medications in the COVID-19 context.

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Section: Discussionmentioning

confidence: 99%

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

2020

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“…An increasing number of lincRNAs have been identified through sequencing in recent years, and many studies have indicated that lincRNAs are an important regulator of skeletal muscle growth and development [9]. In addition, a number of studies have shown that certain lincRNAs play important roles in different biological processes and pathways, such as TLR and inflammatory signaling, T cell activation [10], apoptotic process, negative regulation of cell proliferation [11], and actin cytoskeleton reorganization [12]. Many lincRNAs have been identified in mice and humans; however, some of these lincRNAs remain unidentified in pigs [13,14].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis Reveals Long Intergenic Non-Coding RNAs Contributed to Intramuscular Fat Content Differences between Yorkshire and Wei Pigs

Huang

Zhao

et al. 2020

IJMS

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Intramuscular fat (IMF) content is closely related to various meat traits, such as tenderness, juiciness, and flavor. The IMF content varies considerably among pig breeds with different genetic backgrounds. Long intergenic non-coding RNAs (lincRNAs) have been widely identified in many species and found to be an important class of regulators that can participate in multiple biological processes. However, the mechanism behind lincRNAs regulation of pig IMF content remains unknown and requires further study. In our study, we identified a total of 156 lincRNAs in the longissimus dorsi muscle of Wei (fat-type) and Yorkshire (lean-type) pigs using previously published data. These identified lincRNAs have shorter transcript length, longer exon length, lower exon number, and lower expression level as compared with protein-coding transcripts. We predicted potential target genes (PTGs) that are potentially regulated by lincRNAs in cis or trans regulation. Gene ontology and pathway analyses indicated that many potential lincRNAs target genes are involved in IMF-related processes or pathways, such as fatty acid catabolic process and adipocytokine signaling pathway. In addition, we analyzed quantitative trait locus (QTL) sites that differentially expressed lincRNAs (DE lincRNAs) between Wei and Yorkshire pigs co-localized. The QTL sites where DE lincRNAs co-localize are mostly related to IMF content. Furthermore, we constructed a co-expressed network between DE lincRNAs and their differentially expressed PTGs (DEPTGs). On the basis of their expression levels, we suggest that many DE lincRNAs can affect IMF development by positively or negatively regulating their PTGs. This study identified and analyzed some lincRNAs- and PTGs-related IMF development of the two pig breeds and provided new insight into research on the roles of lincRNAs in the two types of breeds.

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“…On the other side, there are some reports revealed that the lncRNA plays a critical role in different physiological processes in human body [19][20][21]. And the level of lncRNA AK094457 was higher in the hypertensive rats, however, the expression of the lncRNA AK094457 was suppressed after these rats were treated with the notoginsenoside R1 [14].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Long Noncoding RNA (lncRNA) AK094457 Relieved Angiotensin II Induced Vascular Endothelial Cell Injury

Sun

2020

Med Sci Monit

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Departmental sources Background: Hypertension could induce many serious diseases, including damage to vascular endothelial cells. As a noncoding RNA, long noncoding RNA (lncRNA) has received much attention in scientific research and has a regulating efficacy on many critical life activities in human body. The level of lncRNA AK094457 is thought to be elevated in hypertensive rats. However, there is no research indicating the relationship between the level of lncRNA AK094457 and vascular endothelial injury. Material/Methods: In our study, we used lentiviral to knockdown lncRNA AK094457, and the human umbilical vein endothelial cells (HUVECs) were stimulated by the Ang II to imitate the vascular endothelial cell damage caused by hypertension. The Cell Counting Kit-8 assays were used to detect the cells viability. Western blotting was performed to detect the endothelial nitric oxide synthase (eNOS), p-eNOS and endothelin-1 (ET-1). After that the production of the NO was monitored. At last, the reactive oxygen species (ROS) levels and apoptosis rates were detected in this study. Results: According to the results, we found that knockdown lncRNA AK094457 could alleviate the decrease of vascular endothelial cell viability induced by angiotensin II (Ang II). The knockdown of lncRNA AK094457 also relieved the downregulation of eNOS and p-eNOS, and the decreasing of NO release. At the same time, the knockdown of lncRNA inhibited the levels of Ang II-induced proinflammatory cytokines (tumor necrosis factor [TNF]-a, interleukin [IL]-1, and IL-6) and cell adhesion molecules (vascular cell adhesion molecule 1 [VCAM-1], intercellular adhesion molecule 1 [ICAM-1], and monocyte chemoattractant protein-1 [MCP-1]). The levels of ROS and apoptosis rates also decreased after the knockdown of lncRNA AK094457. Conclusions: All these results indicated that lncRNA AK094457 could promote Ang II-induced vascular endothelial cell injury. On the contrary, knockdown of lncRNA AK094457 could alleviate this damage.

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Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination

Cited by 57 publications

References 63 publications

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

Transcriptome Analysis Reveals Long Intergenic Non-Coding RNAs Contributed to Intramuscular Fat Content Differences between Yorkshire and Wei Pigs

Knockdown of Long Noncoding RNA (lncRNA) AK094457 Relieved Angiotensin II Induced Vascular Endothelial Cell Injury

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