Physiological and Pathological Function of Serine/Arginine-Rich Splicing Factor 4 and Related Diseases

Tan, Wanyan; Wang, Wei; Ma, Qingfeng

doi:10.1155/2018/3819719

Cited by 18 publications

(11 citation statements)

References 57 publications

(73 reference statements)

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“…Upregulated genes in RNA splicing categories encode core spliceosomal proteins 60 , including RBM39, Snrnp200, Hnrnpn, Srsf3 and Srsf4. Upregulation of these factors has been previously linked to an increased rate of proliferation [61][62][63] . Similarly, the most strongly upregulated genes associated with DNA binding, chromatin and other significant transcriptional regulation terms include many regulators of proliferation (Hmgb2, Top2a, Mcm7, Pcna) and of neuron differentiation (Insm1, Dlx2, Tead1, Tshz1, Tcf12) [64][65][66] .…”

Section: Fmrp Loss Impacts Neuronal Homeostasismentioning

confidence: 99%

Single Cell Transcriptomics Reveals Dysregulated Cellular and Molecular Networks in a Fragile X Syndrome model

Donnard

Shu

Garber

2020

Preprint

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Despite advances in understanding the pathophysiology of Fragile X syndrome (FXS), its molecular bases are still poorly understood. Whole brain tissue expression profiles have proved surprisingly uninformative. We applied single cell RNA sequencing to profile a FXS mouse model. We found that FXS results in a highly cell type specific effect and it is strongest among different neuronal types. We detected a downregulation of mRNAs bound by FMRP and this effect is prominent in neurons. Metabolic pathways including translation are significantly upregulated across all cell types with the notable exception of excitatory neurons. These effects point to a potential difference in the activity of mTOR pathways, and together with other dysregulated pathways suggest an excitatory-inhibitory imbalance in the FXS cortex which is exacerbated by astrocytes. Our data demonstrate the cell-type specific complexity of FXS and provide a resource for interrogating the biological basis of this disorder.

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Section: Fmrp Loss Impacts Neuronal Homeostasismentioning

confidence: 99%

Single Cell Transcriptomics Reveals Dysregulated Cellular and Molecular Networks in a Fragile X Syndrome model

Donnard

Shu

Garber

2020

Preprint

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“…Plants respond to abiotic and biotic stresses and developmental stimuli by transcriptional reprogramming through constitutive and alternative RNA splicing events. RNA splicing is a highly ordered and dynamic posttranscriptional modification [1] catalyzed by a highly conserved ribonucleoprotein complex known as the spliceosome comprising five small nuclear ribonucleoproteins (snRNPs) (U1, U2, U4/U6, and U5) and numerous non-snRNP proteins, including serine/arginine-rich (SR) proteins [2,3]. The SR proteins have a modular structure (20 to 75 kDa) consisting of one or two N-terminal RNA recognition motifs (RRMs) and serine and arginine-rich C-terminal domains (RS domains with multiple RS dipeptide repeats) [4] that can bind and interact with target pre-mRNAs and proteins to modulate splicing [5].…”

Section: Introductionmentioning

confidence: 99%

“…The phosphorylation and/or dephosphorylation of the RS domain alters the binding affinity of SR proteins for pre-mRNAs and other proteins, thus affecting splicing differently [8]. Protein kinases phosphorylate SR proteins, which initiate spliceosome complex formation [3]. The spliceosome performs the two transesterification reactions that are necessary to excise introns and join together the selected exons [1].…”

Section: Introductionmentioning

confidence: 99%

Brassica Rapa SR45a Regulates Drought Tolerance via the Alternative Splicing of Target Genes

Muthusamy

Yoon

Kim

et al. 2020

Genes

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The emerging evidence has shown that plant serine/arginine-rich (SR) proteins play a crucial role in abiotic stress responses by regulating the alternative splicing (AS) of key genes. Recently, we have shown that drought stress enhances the expression of SR45a (also known as SR-like 3) in Brassica rapa. Herein, we unraveled the hitherto unknown functions of BrSR45a in drought stress response by comparing the phenotypes, chlorophyll a fluorescence and splicing patterns of the drought-responsive genes of Arabidopsis BrSR45a overexpressors (OEs), homozygous mutants (SALK_052345), and controls (Col-0). Overexpression and loss of function did not result in aberrant phenotypes; however, the overexpression of BrSR45a was positively correlated with drought tolerance and the stress recovery rate in an expression-dependent manner. Moreover, OEs showed a higher drought tolerance index during seed germination (38.16%) than the control lines. Additionally, the overexpression of BrSR45a induced the expression of the drought stress-inducible genes RD29A, NCED3, and DREB2A under normal conditions. To further illustrate the molecular linkages between BrSR45a and drought tolerance, we investigated the AS patterns of key drought-tolerance and BrSR45a interacting genes in OEs, mutants, and controls under both normal and drought conditions. The splicing patterns of DCP5, RD29A, GOLS1, AKR, U2AF, and SDR were different between overexpressors and mutants under normal conditions. Furthermore, drought stress altered the splicing patterns of NCED2, SQE, UPF1, U4/U6-U5 tri-snRNP-associated protein, and UPF1 between OEs and mutants, indicating that both overexpression and loss of function differently influenced the splicing patterns of target genes. This study revealed that BrSR45a regulates the drought stress response via the alternative splicing of target genes in a concentration-dependent manner.

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“…SRSF4 was significantly upregulated only in the ILN of LW pigs in response to PRRSV infection, but there was no significant change in TC pigs. SRSF4 was reported to act as a splicing regulator of Caspase-8 and mediates Caspase-8 induced apoptosis as a proapoptotic protease [52]. SRSF4 can regulate alternative splicing induced by cisplatin and contribute to apoptosis [53].…”

Section: Discussionmentioning

confidence: 99%

Global Analysis of Alternative Splicing Difference in Peripheral Immune Organs between Tongcheng Pigs and Large White Pigs Artificially Infected with PRRSV In Vivo

Zhang

Xue

Hang

et al. 2020

BioMed Research International

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Alternative splicing (AS) plays a significant role in regulating gene expression at the transcriptional level in eukaryotes. Flexibility and diversity of transcriptome and proteome can be significantly increased through alternative splicing of genes. In the present study, transcriptome data of peripheral immune organs including spleen and inguinal lymph nodes (ILN) were used to identify AS difference between PRRSV-resistant Tongcheng (TC) pigs and PRRSV-susceptible Large White (LW) pigs artificially infected with porcine reproductive and respiratory syndrome virus (PRRSV) in vivo. The results showed that PRRSV infection induced global alternative splicing events (ASEs) with different modes. Among them, 373 genes and 595 genes in the spleen and ILN of TC pigs, while 458 genes and 560 genes in the spleen and ILN of LW pigs had significantly differential ASEs. Alternative splicing was subject to tissue-specific and lineage-specific regulation in response to PRRSV infection. Enriched GO terms and pathways showed that genes with differential ASEs played important roles in transcriptional regulation, immune response, metabolism, and apoptosis. Furthermore, a splicing factor associated with apoptosis, SRSF4, was significantly upregulated in LW pigs. Functional analysis on apoptosis associated genes was validated by RT-PCR and DNA sequencing. These findings revealed different response to PRRSV between PRRSV-resistant TC pigs and PRRSV-susceptible LW pigs at the level of alternative splicing, suggesting the potential relationship between AS and disease resistance to PRRSV.

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Physiological and Pathological Function of Serine/Arginine-Rich Splicing Factor 4 and Related Diseases

Cited by 18 publications

References 57 publications

Single Cell Transcriptomics Reveals Dysregulated Cellular and Molecular Networks in a Fragile X Syndrome model

Single Cell Transcriptomics Reveals Dysregulated Cellular and Molecular Networks in a Fragile X Syndrome model

Brassica Rapa SR45a Regulates Drought Tolerance via the Alternative Splicing of Target Genes

Global Analysis of Alternative Splicing Difference in Peripheral Immune Organs between Tongcheng Pigs and Large White Pigs Artificially Infected with PRRSV In Vivo

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