Unraveling the Pathways to Neuronal Homeostasis and Disease: Mechanistic Insights into the Role of RNA-Binding Proteins and Associated Factors

Ravanidis, Stylianos; Kattan, Fedon-Giasin; Doxakis, Epaminondas

doi:10.3390/ijms19082280

Cited by 53 publications

(73 citation statements)

References 443 publications

(570 reference statements)

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“…However, following exposure to acute stress, Staufen protein levels increase, thereby increasing cellular sensitivity to apoptosis. Analogously, Staufen overabundance contributes to aberrant translation, ribostasis, and proteostasis ( Ravanidis et al, 2018 ; Gandelman et al, 2020 ). This indicates that both knockdown and overexpression of Staufen can impair synaptic plasticity, and suggests that the relationship between Staufen expression and synaptic plasticity is complex ( Timmerman et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of Embryonic Inflammation and Adolescent Psychosocial Environment on Cognition and Hippocampal Staufen in Middle-Aged Mice

Zhang

et al. 2020

Front. Aging Neurosci.

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Accumulating evidence has indicated that embryonic inflammation could accelerate age-associated cognitive impairment, which can be attributed to dysregulation of synaptic plasticity-associated proteins, such as RNA-binding proteins (RBPs). Staufen is a double-stranded RBP that plays a critical role in the modulation of synaptic plasticity and memory. However, relatively few studies have investigated how embryonic inflammation affects cognition and neurobiology during aging, or how the adolescent psychosocial environment affects inflammation-induced remote cognitive impairment. Consequently, the aim of this study was to investigate whether these adverse factors can induce changes in Staufen expression, and whether these changes are correlated with cognitive impairment. In our study, CD-1 mice were administered lipopolysaccharides (LPS, 50 µg/kg) or an equal amount of saline (control) intraperitoneally during days 15-17 of gestation. At 2 months of age, male offspring were randomly exposed to stress (S), an enriched environment (E), or not treated (CON) and then assigned to five groups: LPS, LPS+S, LPS+E, CON, and CON+S. Mice were evaluated at 3-month-old (young) and 15-month-old (middle-aged). Cognitive function was assessed using the Morris water maze test, while Staufen expression was examined at both the protein and mRNA level using immunohistochemistry/western blotting and RNAscope technology, respectively. The results showed that the middle-aged mice had worse cognitive performance and higher Staufen expression than young mice. Embryonic inflammation induced cognitive impairment and increased Staufen expression in the middle-aged mice, whereas adolescent stress/an enriched environment would accelerated/mitigated these effects. Meanwhile, Staufen expression was closely correlated with cognitive performance. Our findings suggested embryonic inflammation can accelerate age-associated learning and memory impairments, and these effects may be related to the Staufen expression.

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Section: Discussionmentioning

confidence: 99%

Effects of Embryonic Inflammation and Adolescent Psychosocial Environment on Cognition and Hippocampal Staufen in Middle-Aged Mice

Zhang

et al. 2020

Front. Aging Neurosci.

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“…Bio-protocol 10(02): e3488. DOI:10.21769/BioProtoc.3488 12. Dilute the cDNAs with nuclease-free water to 100 μl final volume (1:5 dilution).…”

Section: Daymentioning

confidence: 99%

“…Bio-protocol 10(02): e3488. DOI:10.21769/BioProtoc.3488 12. Maxima TM reverse transcriptase (Thermo Fisher Scientific, catalog number: EP0741) and 5x RT buffer (provided with Maxima Reverse Transcriptase) 13.…”

mentioning

confidence: 99%

Ribonucleoprotein Immunoprecipitation (RIP) Analysis

Martindale¹,

Gorospe²,

Idda³

2020

BIO-PROTOCOL

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RNAs and RNA-binding proteins (RBPs) can interact dynamically in ribonucleoprotein (RNP) complexes that play important roles in controlling gene expression programs. One of the powerful ways to investigate changes in the association of RNAs with an RBP of interest is by immunoprecipitation (IP) analysis of native RNPs. RIP (RNP immunoprecipitation) analysis enables the rapid identification of endogenous RNAs bound to an RBP and to monitor time-dependent changes in this association, as well as changes in response to different metabolic and stress conditions. The protocol is based on the use of an antibody, typically an anti-RBP antibody, to immunoprecipitate the RNP complex. The RNA within the immunoprecipitated complex can then be isolated and further studied using different approaches such as PCR, microarray, Northern blot, and sequencing analyses. Among other advantages, RIP analysis (i) measures RNP associations in many samples relatively quickly, (ii) can be adapted easily to different endogenous RBPs, and (iii) provides extensive information at low cost. Among its limitations, RIP analysis does not inform on the specific sites of interaction of an RBP with a given target RNAs, although recent adaptations of RIP have been developed to overcome this problem. Here we provide an optimized protocol for RIP analysis that can be used to study RNA-protein interactions relevant to many areas of biology.

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“…In silico approaches were utilized to identify potential biological roles for the deregulated circRNAs by identifying the RBPs and miRNAs that are sequestered preferentially by them. [63][64][65][66][67][68][69][70][71][72] .…”

Section: Circrna-rbp and Circrna-mir Interactionsmentioning

confidence: 99%

Differentially expressed circular RNAs in peripheral blood mononuclear cells of PD patients

Ravanidis

Bougea

Karampatsi

et al. 2020

Preprint

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BackgroundNew noninvasive and affordable molecular approaches that will complement current practices and increase the accuracy of PD diagnosis are urgently needed. CircRNAs are highly stable non-coding RNAs that accumulate with aging in neurons and are increasingly shown to regulate all aspects of neuronal development and function.ObjectivesThe aims of the present study were to identify differentially expressed circRNAs in PBMCs of idiopathic PD patients and explore the competing endogenous RNA networks affected.MethodsEighty-seven circRNAs were initially selected based on relatively high gene expression in the human brain. Over half of these were readily detectable in PBMCs using RT-qPCR. Comparative expression analysis was then performed in PBMCs from sixty controls and sixty idiopathic subjects with PD.ResultsSix circRNAs derived from MAPK9, HOMER1, SLAIN1, DOP1B, REPS1, and PSEN1 transcripts were significantly downregulated in PD patients. The classifier that best distinguished PD consisted of four circRNAs with an AUC of 0.84. CLIP-Seq data revealed that the RNA binding proteins bound by most of the deregulated circRNAs include the neurodegeneration-associated FUS, TDP43, FMR1 and ATXN2. MicroRNAs predicted to be sequestered by most deregulated circRNAs had the GOslim categories ‘Protein modification’, ‘Transcription factor activity’ and ‘Cytoskeletal protein binding’ mostly enriched.ConclusionsThis is the first study that identifies circRNAs deregulated in the peripheral blood of PD patients. They may serve as diagnostic biomarkers and since they are highly expressed in the brain and are derived from genes with essential brain functions, they may also hint on the PD pathways affected.

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Unraveling the Pathways to Neuronal Homeostasis and Disease: Mechanistic Insights into the Role of RNA-Binding Proteins and Associated Factors

Cited by 53 publications

References 443 publications

Effects of Embryonic Inflammation and Adolescent Psychosocial Environment on Cognition and Hippocampal Staufen in Middle-Aged Mice

Effects of Embryonic Inflammation and Adolescent Psychosocial Environment on Cognition and Hippocampal Staufen in Middle-Aged Mice

Ribonucleoprotein Immunoprecipitation (RIP) Analysis

Differentially expressed circular RNAs in peripheral blood mononuclear cells of PD patients

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