scholarly journals Rice Transcriptome Analysis Reveals Nitrogen Starvation Modulates Differential Alternative Splicing and Transcript Usage in Various Metabolism-Related Genes

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 285
Author(s):  
Saurabh Chaudhary ◽  
Meenu Kalkal
Keyword(s):  
Alternative Splicing ◽  
Fine Tuning ◽  
Differentially Expressed ◽  
Environmental Damage ◽  
Dependent Manner ◽  
Transcriptional Dynamics ◽  
Crop Varieties ◽  
Alternatively Spliced ◽  
Use Efficiency ◽  
N Starvation

Nitrogen (N) is crucial for plant growth and development; however, excessive use of N fertilizers cause many problems including environmental damage, degradation of soil fertility, and high cost to the farmers. Therefore, immediate implementation is required to develop N efficient crop varieties. Rice being low nitrogen use efficiency (NUE) and a high demand staple food across the world has become a favorite crop to study the NUE trait. In the current study, we used the publicly available transcriptome data generated from the root and shoot tissues of two rice genotypes IR-64 and Nagina-22 (N-22) under optimum N supply (N+) and chronic N-starvation (N−). A stringent pipeline was applied to detect differentially expressed genes (DEGs), alternatively spliced (DAS) genes, differentially expressed transcripts (DETs) and differential transcript usage (DTU) transcripts in both the varieties and tissues under N+ and N− conditions. The DAS genes and DTU transcripts identified in the study were found to be involved in several metabolic and biosynthesis processes. We suggest alternative splicing (AS) plays an important role in fine-tuning the regulation of metabolic pathways related genes in genotype, tissue, and condition-dependent manner. The current study will help in understanding the transcriptional dynamics of NUE traits in the future.

scholarly journals Multi-level regulation of PKCδI alternative splicing by lithium chloride

2020 ◽  
Author(s):  
Deena Bader ◽  
Rekha S. Patel ◽  
Ashley Lui ◽  
Chetna Thawani ◽  
Rea Rupani ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Lithium Chloride ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Fine Tuning ◽  
Serine Threonine Kinase ◽  
Rna Immunoprecipitation ◽  
Alternatively Spliced ◽  
Licl Treatment ◽  
Lncrna Neat1

Lithium chloride (LiCl) is commonly used in treatment of mood disorders, however its usage leads to weight gain which promotes metabolic disorders. Protein Kinase C delta (PKCδ), a serine/threonine kinase, is alternatively spliced to PKCδI and PKCδII in 3T3L1 cells. We previously demonstrated that PKCδI is the predominantly expressed isoform in 3T3L1 pre-adipocytes. Here, we demonstrate that LiCl treatment decreases PKCδI levels, increases formation of lipid droplets and increases oxidative stress. Hence, we investigated the molecular mechanisms underlying the regulation of PKCδI alternative splicing by LiCl. We previously demonstrated that the splice factor SFRS10 is essential for PKCδI splicing. Our results demonstrate that GSK3ß phosphorylates SFRS10 and SFRS10 is in a complex with long noncoding RNA NEAT1 to promote PKCδI splicing. Using PKCδ splicing minigene and RNA-immunoprecipitation assays, our results demonstrate that upon LiCl treatment, NEAT1 levels are reduced, GSK3ß activity is inhibited and SFRS10 phosphorylation is decreased which leads to decreased expression of PKCδI. Integration of the GSK3ß signaling pathway with the ribonucleoprotein complex of lncRNA NEAT1 and SFRS10 enables fine tuning of PKCδI expression during adipogenesis. Knowledge of the molecular pathways impacted by LiCl provide an understanding of the ascent of obesity as a comorbidity in disease management.

scholarly journals The Atypical Kinase RIOK3 Limits RVFV Propagation and Is Regulated by Alternative Splicing

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 367
Author(s):  
Katherine E. Havranek ◽  
Luke Adam White ◽  
Thomas C. Bisom ◽  
Jean-Marc Lanchy ◽  
J. Stephen Lodmell
Keyword(s):  
Alternative Splicing ◽  
Mammalian Cells ◽  
Rift Valley Fever Virus ◽  
Critical Role ◽  
Fine Tuning ◽  
Interferon Response ◽  
Type I ◽  
Interferon Signaling ◽  
Valley Fever ◽  
Alternatively Spliced

In recent years, transcriptome profiling studies have identified changes in host splicing patterns caused by viral invasion, yet the functional consequences of the vast majority of these splicing events remain uncharacterized. We recently showed that the host splicing landscape changes during Rift Valley fever virus MP-12 strain (RVFV MP-12) infection of mammalian cells. Of particular interest, we observed that the host mRNA for Rio Kinase 3 (RIOK3) was alternatively spliced during infection. This kinase has been shown to be involved in pattern recognition receptor (PRR) signaling mediated by RIG-I like receptors to produce type-I interferon. Here, we characterize RIOK3 as an important component of the interferon signaling pathway during RVFV infection and demonstrate that RIOK3 mRNA expression is skewed shortly after infection to produce alternatively spliced variants that encode premature termination codons. This splicing event plays a critical role in regulation of the antiviral response. Interestingly, infection with other RNA viruses and transfection with nucleic acid-based RIG-I agonists also stimulated RIOK3 alternative splicing. Finally, we show that specifically stimulating alternative splicing of the RIOK3 transcript using a morpholino oligonucleotide reduced interferon expression. Collectively, these results indicate that RIOK3 is an important component of the mammalian interferon signaling cascade and its splicing is a potent regulatory mechanism capable of fine-tuning the host interferon response.

scholarly journals PKC Regulates YAP Expression through Alternative Splicing of YAP 3′UTR Pre-mRNA by hnRNP F

2021 ◽  
Vol 22 (2) ◽  
pp. 694
Author(s):  
Wing-Keung Chu ◽  
Li-Man Hung ◽  
Chun-Wei Hou ◽  
Jan-Kan Chen
Keyword(s):  
Alternative Splicing ◽  
Mrna Stability ◽  
Nuclear Translocation ◽  
Human Cancer ◽  
Ectopic Expression ◽  
Full Length ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Alternatively Spliced ◽  
Hnrnp F

The Yes-associated protein (YAP) is a transcriptional co-activator that plays critical roles in organ development and tumorigenesis, and is verified to be inhibited by the Hippo signaling pathway. In the present study, we show that the YAP 3′UTR is alternatively spliced to generate a novel 950 bp 3′UTR mRNA from the full length 3′UTR region (3483 bp) in human cancer cells. The ratio of full length 3′UTR YAP mRNA to alternatively spliced 3′UTR YAP mRNA is up-regulated by exposure of the cells to PKC inhibitor chelerythrine chloride. Further study using luciferase reporter assay showed that the expression of the alternatively spliced 3′UTR mRNA is much lower compared with the full length 3′UTR mRNA, suggesting that alternatively spliced 3′UTR YAP mRNA may have a shorter half-life than full length 3′UTR mRNA. Interestingly, PKC represses YAP 3′UTR–mediated mRNA stability is dependent on a splicing factor, hnRNP F. Activation of PKC induces nuclear translocation of cytosolic hnRNP F. Ectopic expression of hnRNP F enhances YAP 3′UTR splicing. Our results suggest that hnRNP F regulates YAP 3′UTR-mediated mRNA stability in an alternative splicing-dependent manner, and PKC regulated YAP expression is dependent on nuclear translocation of hnRNP F in human cancer cell lines.

scholarly journals The Landscape of Alternative Splicing Regulating Potassium Use Efficiency in Nicotiana tabacum

2021 ◽  
Vol 12 ◽  
Author(s):  
Bing He ◽  
Lin Meng ◽  
Lina Tang ◽  
Weicong Qi ◽  
Fengqin Hu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Nicotiana Tabacum ◽  
Root System ◽  
System Architecture ◽  
Root System Architecture ◽  
Physiological Analysis ◽  
Alternatively Spliced ◽  
Potassium Use Efficiency ◽  
Use Efficiency ◽  
Low K

Alternative splicing (AS) occurs extensively in eukaryotes as an essential mechanism for regulating transcriptome complexity and diversity, but the AS landscape regulating potassium (K) use efficiency in plants is unclear. In this study, we performed high-throughput transcriptome sequencing of roots and shoots from allopolyploid Nicotiana tabacum under K+ deficiency. Preliminary physiological analysis showed that root system architecture was dramatically changed due to potassium deficiency and that IAA content was significantly reduced in root and shoot. AS analysis showed that a total of 28,179 genes exhibited 54,457 AS events, and 1,510 and 1,732 differentially alternatively spliced (DAS) events were identified in shoots and roots under low K+ stress. Nevertheless, only 120 DAS events occurred in both shoots and roots, implying that most DAS events were tissue-specific. Both in shoot and the root, the proportion of DAS genes in differentially expressed (DE) genes equaled that in non-DE genes, which indicated that AS might play a unique regulatory role in response to low potassium. Gene ontology analysis further indicated that transcription regulation and AS modulation worked independently in response to low K+ stress in tobacco, as their target biological processes were different. Totally 45 DAS transcription factors (TFs) were found, which were involved in 18 TF families. Five Auxin response factor (ARF) TFs were significantly DAS in root, suggesting that response to auxin was probably subject to AS regulation in the tobacco root. Our study shows that AS variation occurs extensively and has a particular regulatory mechanism under K+ deficiency in tobacco. The study also links changes in root system architecture with the changes in AS of ARF TFs, which implied the functional significance of these AS events for root growth and architecture.

scholarly journals Splicing-associated chromatin signatures: a combinatorial and position-dependent role for histone marks in splicing definition

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
E. Agirre ◽  
A. J. Oldfield ◽  
N. Bellora ◽  
A. Segelle ◽  
R. F. Luco
Keyword(s):  
Alternative Splicing ◽  
Rna Binding ◽  
Embryonic Stem ◽  
Chromatin Modifications ◽  
Histone Marks ◽  
Splicing Regulators ◽  
Machine Learning Approach ◽  
Alternatively Spliced ◽  
Rna Motif ◽  
Regulation Changes

AbstractAlternative splicing relies on the combinatorial recruitment of splicing regulators to specific RNA binding sites. Chromatin has been shown to impact this recruitment. However, a limited number of histone marks have been studied at a global level. In this work, a machine learning approach, applied to extensive epigenomics datasets in human H1 embryonic stem cells and IMR90 foetal fibroblasts, has identified eleven chromatin modifications that differentially mark alternatively spliced exons depending on the level of exon inclusion. These marks act in a combinatorial and position-dependent way, creating characteristic splicing-associated chromatin signatures (SACS). In support of a functional role for SACS in coordinating splicing regulation, changes in the alternative splicing of SACS-marked exons between ten different cell lines correlate with changes in SACS enrichment levels and recruitment of the splicing regulators predicted by RNA motif search analysis. We propose the dynamic nature of chromatin modifications as a mechanism to rapidly fine-tune alternative splicing when necessary.

scholarly journals GABA signalling modulates stomatal opening to enhance plant water use efficiency and drought resilience

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo Xu ◽  
Yu Long ◽  
Xueying Feng ◽  
Xujun Zhu ◽  
Na Sai ◽  
...  
Keyword(s):  
Water Use Efficiency ◽  
Water Use ◽  
Guard Cell ◽  
Plant Stress ◽  
Stomatal Opening ◽  
Fine Tuning ◽  
Protein Amino Acid ◽  
Gaba Production ◽  
Anion Transporter ◽  
Use Efficiency

AbstractThe non-protein amino acid γ-aminobutyric acid (GABA) has been proposed to be an ancient messenger for cellular communication conserved across biological kingdoms. GABA has well-defined signalling roles in animals; however, whilst GABA accumulates in plants under stress it has not been determined if, how, where and when GABA acts as an endogenous plant signalling molecule. Here, we establish endogenous GABA as a bona fide plant signal, acting via a mechanism not found in animals. Using Arabidopsis thaliana, we show guard cell GABA production is necessary and sufficient to reduce stomatal opening and transpirational water loss, which improves water use efficiency and drought tolerance, via negative regulation of a stomatal guard cell tonoplast-localised anion transporter. We find GABA modulation of stomata occurs in multiple plants, including dicot and monocot crops. This study highlights a role for GABA metabolism in fine tuning physiology and opens alternative avenues for improving plant stress resilience.

scholarly journals Decoding the temporal nature of brain GR activity in the NFκB signal transition leading to depressive-like behavior

2021 ◽  
Author(s):  
Young-Min Han ◽  
Min Sun Kim ◽  
Juyeong Jo ◽  
Daiha Shin ◽  
Seung-Hae Kwon ◽  
...  
Keyword(s):  
Inhibitory Action ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Late Phase ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Middle Phase ◽  
Temporal Shift

AbstractThe fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.

scholarly journals Regulation of CD44 Alternative Splicing by SRm160 and Its Potential Role in Tumor Cell Invasion

2006 ◽  
Vol 26 (1) ◽  
pp. 362-370 ◽  
Author(s):  
Chonghui Cheng ◽  
Phillip A. Sharp
Keyword(s):  
Alternative Splicing ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Rna Splicing ◽  
Tumor Cell Invasion ◽  
Dependent Manner ◽  
Cd44 Isoforms ◽  
Transmembrane Glycoprotein ◽  
Cell Invasiveness ◽  
Interfering Rna

ABSTRACT The multiple isoforms of the transmembrane glycoprotein CD44 are produced by alternative RNA splicing. Expression of CD44 isoforms containing variable 5 exon (v5) correlates with enhanced malignancy and invasiveness of some tumors. Here we demonstrate that SRm160, a splicing coactivator, regulates CD44 alternative splicing in a Ras-dependent manner. Overexpression of SRm160 stimulates inclusion of CD44 v5 when Ras is activated. Conversely, small interfering RNA (siRNA)-mediated silencing of SRm160 significantly reduces v5 inclusion. Immunoprecipitation shows association of SRm160 with Sam68, a protein that also stimulates v5 inclusion in a Ras-dependent manner, suggesting that these two proteins interact to regulate CD44 splicing. Importantly, siRNA-mediated depletion of CD44 v5 decreases tumor cell invasion. Reduction of SRm160 by siRNA transfection downregulates the endogenous levels of CD44 isoforms, including v5, and correlates with a decrease in tumor cell invasiveness.

scholarly journals Regulation of Wnt Signaling by FOX Transcription Factors in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3446
Author(s):  
Stefan Koch
Keyword(s):  
Transcription Factors ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Treatment Options ◽  
Wnt Signaling Pathway ◽  
Tissue Homeostasis ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Forkhead Box ◽  
Signaling Activity

Aberrant activation of the oncogenic Wnt signaling pathway is a hallmark of numerous types of cancer. However, in many cases, it is unclear how a chronically high Wnt signaling tone is maintained in the absence of activating pathway mutations. Forkhead box (FOX) family transcription factors are key regulators of embryonic development and tissue homeostasis, and there is mounting evidence that they act in part by fine-tuning the Wnt signaling output in a tissue-specific and context-dependent manner. Here, I review the diverse ways in which FOX transcription factors interact with the Wnt pathway, and how the ectopic reactivation of FOX proteins may affect Wnt signaling activity in various types of cancer. Many FOX transcription factors are partially functionally redundant and exhibit a highly restricted expression pattern, especially in adults. Thus, precision targeting of individual FOX proteins may lead to safe treatment options for Wnt-dependent cancers.

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