scholarly journals Arabidopsis ACINUS is O-glycosylated and regulates transcription and alternative splicing of regulators of reproductive transitions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yang Bi ◽  
Zhiping Deng ◽  
Weimin Ni ◽  
Ruben Shrestha ◽  
Dasha Savage ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Metabolic Regulation ◽  
Regulation Of Transcription ◽  
Chromatin Remodelers ◽  
Cellular Targets ◽  
Growth Defects ◽  
Rna Interaction ◽  
Glcnac Transferase ◽  
Secret Agent

AbstractO-GlcNAc modification plays important roles in metabolic regulation of cellular status. Two homologs of O-GlcNAc transferase, SECRET AGENT (SEC) and SPINDLY (SPY), which have O-GlcNAc and O-fucosyl transferase activities, respectively, are essential in Arabidopsis but have largely unknown cellular targets. Here we show that AtACINUS is O-GlcNAcylated and O-fucosylated and mediates regulation of transcription, alternative splicing (AS), and developmental transitions. Knocking-out both AtACINUS and its distant paralog AtPININ causes severe growth defects including dwarfism, delayed seed germination and flowering, and abscisic acid (ABA) hypersensitivity. Transcriptomic and protein-DNA/RNA interaction analyses demonstrate that AtACINUS represses transcription of the flowering repressor FLC and mediates AS of ABH1 and HAB1, two negative regulators of ABA signaling. Proteomic analyses show AtACINUS’s O-GlcNAcylation, O-fucosylation, and association with splicing factors, chromatin remodelers, and transcriptional regulators. Some AtACINUS/AtPININ-dependent AS events are altered in the sec and spy mutants, demonstrating a function of O-glycosylation in regulating alternative RNA splicing.

scholarly journals Arabidopsis ACINUS is O-glycosylated and regulates transcription and alternative splicing of regulators of reproductive transitions

2020 ◽  
Author(s):  
Yang Bi ◽  
Zhiping Deng ◽  
Weimin Ni ◽  
Ruben Shretha ◽  
Dasha Savage ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Metabolic Regulation ◽  
Regulation Of Transcription ◽  
Chromatin Remodelers ◽  
Cellular Targets ◽  
Growth Defects ◽  
Rna Interaction ◽  
Glcnac Transferase ◽  
Secret Agent

AbstractO-GlcNAc modification plays important roles in metabolic regulation of cellular status. Two homologs of O-GlcNAc transferase, SECRET AGENT (SEC) and SPINDLY (SPY), which have O-GlcNAc and O-fucosyl transferase activities, respectively, are essential in Arabidopsis but have largely unknown cellular targets. Here we show that AtACINUS is O-GlcNAcylated and O-fucosylated and mediates regulation of transcription, alternative splicing (AS), and developmental transitions. Knocking-out both AtACINUS and its distant paralog AtPININ causes severe growth defects including dwarfism, delayed seed germination and flowering, and abscisic acid (ABA) hypersensitivity. Transcriptomic and protein-DNA/RNA interaction analyses demonstrate that AtACINUS represses transcription of the flowering repressor FLC and mediates AS of ABH1 and HAB1, two negative regulators of ABA signaling. Proteomic analyses show AtACINUS’s O-GlcNAcylation, O-fucosylation, and association with splicing factors, chromatin remodelers, and transcriptional regulators. Some AtACINUS/AtPININ-dependent AS events are altered in the sec and spy mutants, demonstrating a function of O-glycosylation in regulating alternative RNA splicing.

scholarly journals Regulation of transcription of the RNA splicing factor hSlu7 by Elk-1 and Sp1 affects alternative splicing

RNA ◽  
2007 ◽  
Vol 13 (11) ◽  
pp. 1988-1999 ◽  
Author(s):  
M. Alberstein ◽  
M. Amit ◽  
K. Vaknin ◽  
A. O'Donnell ◽  
C. Farhy ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Splicing Factor ◽  
Regulation Of Transcription

Linking transcription, RNA polymerase II elongation and alternative splicing

2020 ◽  
Vol 477 (16) ◽  
pp. 3091-3104 ◽  
Author(s):  
Luciana E. Giono ◽  
Alberto R. Kornblihtt
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Rna Polymerase Ii ◽  
Environmental Changes ◽  
Transcription Elongation ◽  
Single Gene ◽  
Regulation Of Gene Expression ◽  
Regulation Of Transcription ◽  
Stepping Stones ◽  
Eukaryotic Transcription

Gene expression is an intricately regulated process that is at the basis of cell differentiation, the maintenance of cell identity and the cellular responses to environmental changes. Alternative splicing, the process by which multiple functionally distinct transcripts are generated from a single gene, is one of the main mechanisms that contribute to expand the coding capacity of genomes and help explain the level of complexity achieved by higher organisms. Eukaryotic transcription is subject to multiple layers of regulation both intrinsic — such as promoter structure — and dynamic, allowing the cell to respond to internal and external signals. Similarly, alternative splicing choices are affected by all of these aspects, mainly through the regulation of transcription elongation, making it a regulatory knob on a par with the regulation of gene expression levels. This review aims to recapitulate some of the history and stepping-stones that led to the paradigms held today about transcription and splicing regulation, with major focus on transcription elongation and its effect on alternative splicing.

scholarly journals Role of Alternative Splicing in Regulating Host Response to Viral Infection

Cells ◽  
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.

scholarly journals Profiling PRMT methylome reveals roles of hnRNPA1 arginine methylation in RNA splicing and cell growth

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wen-juan Li ◽  
Yao-hui He ◽  
Jing-jing Yang ◽  
Guo-sheng Hu ◽  
Yi-an Lin ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Cell Growth ◽  
Rna Splicing ◽  
Synergistic Effects ◽  
Arginine Methylation ◽  
Type I ◽  
Prostate Cancer Cells ◽  
Cancer Cell Growth ◽  
Cancer Mutations ◽  
Substrate Spectrum

AbstractNumerous substrates have been identified for Type I and II arginine methyltransferases (PRMTs). However, the full substrate spectrum of the only type III PRMT, PRMT7, and its connection to type I and II PRMT substrates remains unknown. Here, we use mass spectrometry to reveal features of PRMT7-regulated methylation. We find that PRMT7 predominantly methylates a glycine and arginine motif; multiple PRMT7-regulated arginine methylation sites are close to phosphorylations sites; methylation sites and proximal sequences are vulnerable to cancer mutations; and methylation is enriched in proteins associated with spliceosome and RNA-related pathways. We show that PRMT4/5/7-mediated arginine methylation regulates hnRNPA1 binding to RNA and several alternative splicing events. In breast, colorectal and prostate cancer cells, PRMT4/5/7 are upregulated and associated with high levels of hnRNPA1 arginine methylation and aberrant alternative splicing. Pharmacological inhibition of PRMT4/5/7 suppresses cancer cell growth and their co-inhibition shows synergistic effects, suggesting them as targets for cancer therapy.

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.

PRMT5 Prevents Dilated Cardiomyopathy via Suppression of Protein O-GlcNAcylation

2021 ◽  
Author(s):  
Zhenhua Li ◽  
Jingping Xu ◽  
Yao Song ◽  
Chong Xin ◽  
Lantao Liu ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Knockout Mice ◽  
Rna Splicing ◽  
Gene Knockout ◽  
Major Type ◽  
Integrated Analysis ◽  
Arginine Methyltransferase ◽  
Potential Strategy ◽  
Glcnac Transferase

Rationale: Protein O-GlcNAcylation is dynamically regulated by two key enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Excessive protein O-GlcNAcylation contributes to dilated cardiomyopathy (DCM), but its regulatory mechanisms are not fully understood. The protein arginine methyltransferase 5 (PRMT5) is the major type II arginine methyltransferase, which plays critical physiological roles by symmetrically dimethylating various downstream targets including proteins involved in RNA splicing. However, its function in regulating protein O-GlcNAcylation and DCM is unexplored. Objective: To elucidate the physiological function of PRMT5 and the mechanism underlying its role in regulating cardiac O-GlcNAcylation and homeostasis. Methods and Results: Conditional gene knockout was used to study the in vivo function of Prmt5 in regulating cardiac homeostasis. An integrated analysis of transcriptomic and metabolomic profiles was performed to investigate the molecular mechanism. Adeno-associated virus 9 (AAV9)-mediated gene delivery in the mouse was used to study the protein O-GlcNAcylation in Prmt5 deficiency-induced DCM. PRMT5 mRNA was decreased in human DCM hearts, and cardiomyocyte-specific Prmt5 deletion in mice resulted in DCM and heart failure. Transcriptomic and metabolomic profiling identified increased O-GlcNAcylation in the hearts of Prmt5-knockout mice. Mechanistically, Prmt5 deletion suppressed O-GlcNAcase (OGA) expression by inhibiting the transcription of Oga and triggering its aberrant splicing. Consistently, a positive correlation of PRMT5 and OGA was identified in human DCM hearts. Notably, gene therapy with AAV9 encoding the correctly spliced Oga normalized the cardiac protein O-GlcNAcylation levels and partially rescued the dilation and dysfunction of the hearts in Prmt5-knockout mice. Conclusions: Our data demonstrate a novel function of PRMT5 in regulating protein O-GlcNAcylation to maintain cardiac homeostasis, suggesting that targeting the PRMT5-OGA axis could be a potential strategy for treating DCM.

cis-acting elements and a trans-acting factor affecting alternative splicing of adenovirus L1 transcripts

1989 ◽  
Vol 9 (10) ◽  
pp. 4364-4371
Author(s):  
C Delsert ◽  
N Morin ◽  
D F Klessig
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Late Phase ◽  
Simian Virus 40 ◽  
Splice Junction ◽  
Simian Virus ◽  
T Antigen ◽  
Expression Vectors ◽  
Acceptor Site ◽  
Proximal Site

Expression of the L1 region of adenovirus is temporally regulated by alternative splicing to yield two major RNAs encoding the 52- to 55-kilodalton (52-55K) and IIIa polypeptides. The distal acceptor site (IIIa) is utilized only during the late phase of infection, whereas the proximal site (52-55K) is used at both early and late times. Several parameters that might affect this alternative splicing were tested by using expression vectors carrying the L1 region or mutated versions of it. In the absence of a virus-encoded or -induced factor(s), only the 52-55K acceptor was used. Decreasing the distance between the donor and the IIIa acceptor had no effect. Removal of the 52-55K acceptor induced IIIa splicing slightly, implying competition between the two acceptors. Fusion of the IIIa exon to the 52-55K intron greatly enhanced splicing of the IIIa junction, suggesting that the IIIa exon does not contain sequences that inhibit splicing. Thus, the lack of splicing to the IIIa acceptor in the absence of a virus-encoded or -induced factor(s) is probably due to the absence of a favorable sequence and/or the presence of a negative element 5' of the IIIa splice junction, or both. The presence of several adenovirus gene products, including VA RNAs, the E2A DNA-binding protein, and the products of E1A and E1B genes, did not facilitate use of the IIIa acceptor. In contrast, the simian virus 40 early proteins, probably large T antigen, induced IIIa splicing. This result, together with those of earlier studies, suggest that T antigen plays a role in modulation of alternative RNA splicing.

scholarly journals DoChaP: The Domain Change Presenter

2020 ◽  
Author(s):  
Shani T. Gal-Oz ◽  
Nimrod Haiat ◽  
Dana Eliyahu ◽  
Guy Shani ◽  
Tal Shay
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Protein Domains ◽  
Visual Presentation ◽  
Structural Effect ◽  
Protein Isoforms ◽  
Multiple Transcripts ◽  
Genome Wide ◽  
Health And Disease ◽  
Specific Alternative

AbstractAlternative RNA splicing results in multiple transcripts of the same gene, possibly encoding for different protein isoforms with different protein domains and functionalities. Whereas it is possible to manually determine the effect of a specific alternative splicing event on the domain composition of a particular encoded protein, the process requires the tedious integration of several data sources; it is therefore error prone and its implementation is not feasible for genome-wide characterization of domains affected by differential splicing. To fulfill the need for an automated solution, we developed the Domain Change Presenter (DoChaP), a web server for the visualization of the exon–domain association. DoChaP visualizes all transcripts of a given gene, the domains of the proteins that they encode, and the exons encoding each domain. The visualization enables a comparison between the transcripts and between the protein isoforms they encode for. The organization and visual presentation of the information makes the structural effect of each alternative splicing event on the protein structure easily identified. To enable a study of the conservation of the exon structure, alternative splicing, and the effect of alternative splicing on protein domains, DoChaP also facilitates an inter-species comparison of domain–exon associations. DoChaP thus provides a unique and easy-to-use visualization of the exon–domain association and its conservation between transcripts and orthologous genes and will facilitate the study of the functional effects of alternative splicing in health and disease.

scholarly journals Metabolic Regulation of Transcription and Chromatin

2018 ◽  
Vol 87 (1) ◽  
pp. 23-25 ◽  
Author(s):  
Ronald C. Conaway
Keyword(s):  
Ribosome Biogenesis ◽  
Metabolic Regulation ◽  
Cell Metabolism ◽  
Rna Polymerases ◽  
Annual Review ◽  
Regulation Of Transcription ◽  
Energy Status ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Biochemical Mechanisms

Although cell metabolism has been established as a major regulator of eukaryotic gene expression, the mechanisms underlying this regulation are still being uncovered. Recent years have seen great advances in our understanding of biochemical mechanisms of metabolic regulation of transcription and chromatin. Prime examples include insights into how nutrients and cellular energy status regulate synthesis of ribosomal RNAs by RNA polymerases I and III during ribosome biogenesis and how a variety of enzymes that catalyze modifications of histones in chromatin are regulated by the levels of certain metabolites. This volume of the Annual Review of Biochemistry includes a set of reviews describing these and other advances in understanding aspects of the metabolic regulation of RNA polymerases I and III transcription and chromatin.

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