Role of CUG-binding proteins in the regulation of alternative splicing of α-tropomyosin and α -actinin gen es

AbstractSeed germination is the process through which a quiescent organ reactivates its metabolism culminating with the resumption cell divisions. It is usually the growth of a plant contained within a seed and results in the formation of a seedling. Post-transcriptional regulation plays an important role in gene expression. In cells, post-transcriptional regulation is mediated by many factors, such as RNA-binding proteins, microRNAs, and the spliceosome. This review provides an overview of the relationship between seed germination and post-transcriptional regulation. It addresses the relationship between seed germination and RNA-binding proteins, microRNAs and alternative splicing. This presentation of the current state of the knowledge will promote new investigations into the relevance of the interactions between seed germination and post-transcriptional regulation in plants.

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Faculty Opinions recommendation of Potential role of DNA methylation as a facilitator of target search processes for transcription factors through interplay with methyl-CpG-binding proteins.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727592293.793537373 ◽

2017 ◽

Author(s):

Martha Bulyk ◽

Raluca Gordan

Keyword(s):

Dna Methylation ◽

Transcription Factors ◽

Binding Proteins ◽

Potential Role ◽

Target Search ◽

Search Processes

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PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3

Cell Death and Disease ◽

10.1038/s41419-021-04013-y ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Dawei Chen ◽

Zhenguo Zhao ◽

Lu Chen ◽

Qinghua Li ◽

Jixue Zou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Alternative Splicing ◽

Protein Function ◽

Vital Role ◽

Normal Tissues ◽

Mechanistic Analysis ◽

Highly Correlated ◽

Splicing Patterns

AbstractEmerging evidence has demonstrated that alternative splicing has a vital role in regulating protein function, but how alternative splicing factors can be regulated remains unclear. We showed that the PPM1G, a protein phosphatase, regulated the phosphorylation of SRSF3 in hepatocellular carcinoma (HCC) and contributed to the proliferation, invasion, and metastasis of HCC. PPM1G was highly expressed in HCC tissues compared to adjacent normal tissues, and higher levels of PPM1G were observed in adverse staged HCCs. The higher levels of PPM1G were highly correlated with poor prognosis, which was further validated in the TCGA cohort. The knockdown of PPM1G inhibited the cell growth and invasion of HCC cell lines. Further studies showed that the knockdown of PPM1G inhibited tumor growth in vivo. The mechanistic analysis showed that the PPM1G interacted with proteins related to alternative splicing, including SRSF3. Overexpression of PPM1G promoted the dephosphorylation of SRSF3 and changed the alternative splicing patterns of genes related to the cell cycle, the transcriptional regulation in HCC cells. In addition, we also demonstrated that the promoter of PPM1G was activated by multiple transcription factors and co-activators, including MYC/MAX and EP300, MED1, and ELF1. Our study highlighted the essential role of PPM1G in HCC and shed new light on unveiling the regulation of alternative splicing in malignant transformation.

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LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM

Molecular Cancer ◽

10.1186/s12943-020-01299-y ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Feifei Zhang ◽

Hui Wang ◽

Jiang Yu ◽

Xueqing Yao ◽

Shibin Yang ◽

...

Keyword(s):

Gastric Cancer ◽

Alternative Splicing ◽

Noncoding Rna ◽

De Novo ◽

Acquired Resistance ◽

Genetic Alterations ◽

Clinical Samples ◽

Autophagy Flux ◽

Resistance To Chemotherapy

AbstractDe novo and acquired resistance, which are mainly mediated by genetic alterations, are barriers to effective routine chemotherapy. However, the mechanisms underlying gastric cancer (GC) resistance to chemotherapy are still unclear. We showed that the long noncoding RNA CRNDE was related to the chemosensitivity of GC in clinical samples and a PDX model. CRNDE was decreased and inhibited autophagy flux in chemoresistant GC cells. CRNDE directly bound to splicing protein SRSF6 to reduce its protein stability and thus regulate alternative splicing (AS) events. We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.

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Role of Alternative Splicing in Regulating Host Response to Viral Infection

Cells ◽

10.3390/cells10071720 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1720

Author(s):

Kuo-Chieh Liao ◽

Mariano A. Garcia-Blanco

Keyword(s):

Innate Immunity ◽

Alternative Splicing ◽

Immune Responses ◽

Viral Infection ◽

Rna Splicing ◽

Type I ◽

Host Immune Responses ◽

Transcriptional Regulatory Mechanisms ◽

Host Virus Interactions

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection. We describe how several central components of the Type I and III interferon pathways encode spliced isoforms to regulate IFN activation and function. Additionally, the functional roles of splicing factors and modulators in antiviral immunity are discussed. Lastly, we discuss how cell death pathways are regulated by alternative splicing as well as the potential role of this regulation on host immunity and viral infection. Altogether, these studies highlight the importance of RNA splicing in regulating host–virus interactions and suggest a role in downregulating antiviral innate immunity; this may be critical to prevent pathological inflammation.

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