RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function

Wang, Hanying; Hsieh, Pei-Fen; Huang, De-Fong; Chin, Pey-Shyuan; Chou, Chih-Hsuan; Tung, Chun-Che; Chen, Shin-Yuan; Lee, Li-Jen; Gau, Susan Shur‐Fen; Huang, Hsiang‐Po

doi:10.1038/srep17383

Cited by 61 publications

(71 citation statements)

References 47 publications

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“…EGR4 is also upregulated in response to trophic factors in an ERK1/2-dependent manner that has been characterized in the context of neuronal development and spermatogenesis [65-67]. While EGR4 appears to compensate for EGR1 in some cases, SRF binding to the EGR4 promoter was shown to occur in neuronal cells [68] supported by indirect evidence that serum may regulate the EGR4 promoter generated in Jurkat T cells [69].…”

Section: Regulation Of Egr Expressionmentioning

confidence: 99%

EGR-mediated control of STIM expression and function

Gross

Hooper

et al. 2019

Cell Calcium

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Summary Ca2+ is a ubiquitous, dynamic and pluripotent second messenger with highly context-dependent roles in complex cellular processes such as differentiation, proliferation, and cell death [1]. These Ca2+ signals are generated by Ca2+-permeable channels located on the plasma membrane (PM) and endoplasmic reticulum (ER) and shaped by PM- and ER-localized pumps and transporters. Differences in the expression of these Ca2+ homeostasis proteins contribute to cell and context-dependent differences in the spatiotemporal organization of Ca2+ signals and, ultimately, cell fate. This review focuses on the Early Growth Response (EGR) family of zinc finger transcription factors and their role in the transcriptional regulation of Stromal Interaction Molecule (STIM1), a critical regulator of Ca2+ entry in both excitable and non-excitable cells.

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Section: Regulation Of Egr Expressionmentioning

confidence: 99%

EGR-mediated control of STIM expression and function

Gross

Hooper

et al. 2019

Cell Calcium

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“…Real-time quantitative PCR was performed using SYBRgreen on a TAKARA detection system (TAKARA, Shiga, Japan) under the conditions recommended by the manufacturer. The primer sequences were as follows (27)(28)(29)(30)(31)(32)(33): angiotensinogen (Agt, NM_007428), forward: 5'-GGC CGC CGA GAA GCT AGA-3' and reverse: 5'-GGC TGG CCG TGG GAT CTA-3'; renin (Renin, NM_031192), forward: 5'-GCC GCC TCT ACC TTG CTT GTG-3' and reverse: 5' GGG GCA GCT CGG TGA CCT CT-3'; angiotensin I converting enzyme (Ace, NM_207624), forward: 5'-AGG GAA CAT GTG GGC GCA GAC-3' and reverse: 5'-CGG TGG GCT TCT CTA ACA TCG A-3'; advanced glycosylation end product-specific receptor (Ager, NM_007425), forward: 5'-TGA GGA GAG GAA GGC CCC G-3' and reverse: 5'-GCC ATC ACA CAG GCT CGA TC-3'; neuronal nuclei (NeuN, NM_001039167), as a marker of neural cells, forward: 5'-GAG GAG TGG CCC GTT CTG-3' and reverse: 5'-AGG CGG AGG AGG GTACTG-3'; glial fibrillary acidic protein (Gfap, NM_010277) , as a marker of astrocytes, forward: 5'-GAA CAA CCT GGC TGC GTA TA-3' and reverse: 5'-GCG ATT CAA CCT TTC TCT CC-3'; cluster of differentiation molecule 11b (CD11b, NM_001082960), as a marker of microglial cells, forward: 5'-GAT CAA CAA TGT GAC CGT ATG-3' and reverse: 5'-GAT CCC GGA AAT TGG AGT GAG-3'; glyceraldehyde 3-phosphate dehydrogenase (Gapdh, NM_008084), forward: 5'-CCG CAT CTT CTT GTG CAG TGC C-3' and reverse: 5'-GGG GTC GTT GAT GGC AAC AAT CTC-3'.…”

Section: Animals Male Diabetic Mice [C57blks(bks) Cg-+ Lepr Db /+mentioning

confidence: 99%

Effects of Diets with Different Proportions of Protein/ Carbohydrate on Retinal Manifestations in db Mice

Emi

Okatani

Araki

et al. 2018

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Abstract. Background Diabetic retinopathy is one of the three major complications of diabetes, and it is the leading cause of visual impairment and blindness among adults (1). A recent epidemiological study found diabetic retinopathy prevalence to be 34.6% for individuals with diabetes (2). In the Wisconsin Epidemiological Study of Diabetic Retinopathy, microalbuminuria, representing nephropathy, was associated with the presence of retinopathy in individuals with diabetes (3). The recent rise in the numbers of diabetes and diabetic retinopathy cases worldwide is likely to be related to lifestyle/life environment rather than genetic factors, as a global genetic diversity has not changed appreciably over this short period of time (4-7). Lifestyle factors, including nutrition, have been altered markedly in recent decades (8, 9). Diabetic nephropathy is aggravated by higher intake of total protein (10, 11). However, the impact of altered nutrition, especially protein content, on the development of diabetic retinopathy is not fully understood (10,11,12).Glycemic control and blood pressure control reduce the progression of diabetic retinopathy, and ophthalmological treatment including laser applications plays a prominent role in the control of diabetic retinopathy. However, currently there are no drugs that inhibit the onset or progression of diabetic retinopathy, except for inhibitors of the renin-angiotensin (RA) system (13-17). Regarding nutritional intervention, patients with diabetic retinopathy have been managed by a low-energy diet of suppressed carbohydrate intake and relatively highprotein intake, but the influence of diet on the pathophysiology of retinopathy is not fully understood. A rodent study of diabetic nephropathy reported an additive effect of RA system inhibitors and a low-protein diet on kidney manifestations (18). A low-protein diet may have additional beneficial effects through suppressed expression of genes involved in the kidney RA system. The effect of dietary protein content diets (12-24% energy), which is the range in regular human diets (4, 8), on glucose levels and renal manifestations in db mice (19,20), an animal model for diabetes with leptin-receptor deficiency. In the experiments using db mice, a high-protein, low-carbohydrate diet increased blood glucose levels and exacerbated renal manifestations, compared with a low-protein, high-carbohydrate diet (21,22). The dietary protein content should be examined for its 265

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“…4b and S3). To further examine a role for Rbfox3 in Snord116 splicing, we utilized a published dataset of RNA sequencing from Rbfox3 knockout mouse cerebral cortex (24). Visualization of exon junctions within the Snord116 locus by sashimi plot using the IGV browser demonstrated that loss of Rbfox3 leads to pronounced dysregulation of exon splicing between Snord116 and Ube3a (Fig.…”

Section: Neuron-specific Splicing Of Transgenic Snord116 Requires Rbfmentioning

confidence: 99%

“…RNA-seq Analysis SRA files were downloaded from GEO (GSE84786) (24) and converted to fastq files using fastq-dump, splitting files for paired-end reads. Reads were trimmed for adapters and quality using the following parameters: ILLUMINACLIP:TruSeq3-PE.fa:2:30:10:8:T LEADING:15 TRAILING:15 SLIDINGWINDOW:4:15.…”

Section: Inverse Pcr Primers: F -Gatttccaagtctccaccccat; R -Ggctatgaamentioning

confidence: 99%

Prader-Willi locus Snord116 RNA processing requires an active endogenous allele and neuron-specific splicing by Rbfox3/NeuN

Coulson

Powell

Yasui

et al. 2018

Preprint

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Prader-Willi syndrome (PWS), an imprinted neurodevelopmental disorder characterized by metabolic, sleep, and neuropsychiatric features, is caused by the loss of paternal SNORD116, containing only noncoding RNAs. The primary SNORD116 transcript is processed into small nucleolar RNAs (snoRNAs), which localize to nucleoli, and their spliced host gene 116HG, which is retained at its site of transcription. While functional complementation of the SNORD116 noncoding RNAs is a desirable goal for treating PWS, the mechanistic requirements of SNORD116 RNA processing are poorly understood. Here we developed and tested a novel transgenic mouse which ubiquitously expresses Snord116 on both a wild-type and Snord116 paternal deletion (Snord116 +/-) background. Interestingly, while the Snord116 transgene was ubiquitously expressed in multiple tissues, splicing of the transgene and production of snoRNAs was limited to brain tissues. Knockdown of Rbfox3, encoding neuron-specific splicing factor NeuN, in Snord116 +/--derived neurons reduced splicing of the transgene in neurons. RNA fluorescent in situ hybridization for 116HG revealed a single significantly larger signal in transgenic mice, demonstrating colocalization of transgenic and endogenous 116HG RNAs. Similarly, significantly increased snoRNA levels were detected in transgenic neuronal nucleoli, indicating that transgenic Snord116 snoRNAs were effectively processed and localized. In contrast, neither transgenic 116HG nor snoRNAs were detectable in either non-neuronal tissues or Snord116 +/neurons. Together, these results demonstrate that exogenous expression and neuron-specific splicing of the Snord116 locus are insufficient to rescue the genetic deficiency of Snord116 paternal deletion. Elucidating the mechanisms regulating Snord116 processing and localization are essential to develop effective gene replacement therapies for PWS.

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RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function

Cited by 61 publications

References 47 publications

EGR-mediated control of STIM expression and function

EGR-mediated control of STIM expression and function

Effects of Diets with Different Proportions of Protein/ Carbohydrate on Retinal Manifestations in db Mice

Prader-Willi locus Snord116 RNA processing requires an active endogenous allele and neuron-specific splicing by Rbfox3/NeuN

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