scholarly journals Secondary Mutation-Induced Alternative Splicing Suppresses RNA Splicing Defect of the jhs1 Mutant

2020 ◽  
Vol 182 (4) ◽  
pp. 2025-2034
Author(s):  
Yiqiong Li ◽  
Xiaomin Liu ◽  
Yuxuan Guo ◽  
Jianbo Xie ◽  
Lulu Wang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Secondary Mutation ◽  
Splicing Defect

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.

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 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

Abstract 124: Fetal-Like RNA Splicing Remodeling in Failing Heart Revealed by Total Transcriptome Analysis

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Chen Gao ◽  
Vincent Ren ◽  
Grace (Xinshu) Xiao ◽  
Jaunian Chen ◽  
Yibin Wang
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Cardiac Development ◽  
Heart Diseases ◽  
Expression Profiles ◽  
Mrna Splicing ◽  
Mouse Heart ◽  
Failing Heart ◽  
Splicing Regulators ◽  
A Genome

The complexity of transcriptome and proteome is contributed by alternative splicing of mRNA. Altered mRNA splicing is also implicated in many human diseases including cancer. However, little knowledge is available about the scope of alternative splicing at whole genome level in heart diseases and even less about the mechanisms underlying the regulation of mRNA splicing in response to pathological injury in heart. Using a genome-wide RNA-Seq analysis, we have identified global alternative splicing changes associated with both development and pathological remodeling in mouse heart. Most significantly, the alternative RNA splicing events observed in failing heart mimicked the splicing profile in fetal hearts, suggesting a fetal like RNA splicing remodeling in failing hearts. After examining the expression profiles of splicing regulators in neonatal, normal adult, and failing adult hearts, Fox-1 was identified as one to be significantly down regulated in the failing and fetal hearts. Morpholino mediated Fox-1 knock-down in zebrafish embryos led to lethal phenotype associated with impaired cardiac development and function. This phenotype could be rescued by re-expressing both zebrafish and mouse Fox1 gene. Therefore, our established functional significance of Fox1 mediated RNA alternative splicing serves as a key molecular player in transcriptome remodeling during cardiac development and pathology.

Alternative RNA splicing that is spatially regulated: generation of transcripts from the Antennapedia gene of Drosophila melanogaster with different protein-coding regions

1988 ◽  
Vol 8 (10) ◽  
pp. 4143-4154
Author(s):  
V L Stroeher ◽  
J C Gaiser ◽  
R L Garber
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Developmental Stages ◽  
Molecular Evidence ◽  
Rnase Protection ◽  
Protein Coding ◽  
Spatial Regulation ◽  
Coding Regions ◽  
Imaginal Disks ◽  
Isolated Tissues

We have shown previously that transcription of the Drosophila homeotic gene Antennapedia results in four major RNA species which differ in long 5'- and 3'-untranslated sequences. The protein-coding portion of these transcripts, however, is located in exons common to all. Using RNase protection assays and further cDNA clone isolation, we have now detected two alternative splicing events between exons of this region. These result in four RNA variations which, if translated, would encode a family of Antennapedia proteins. By analyzing transcripts from various developmental stages and isolated tissues, we show that alternative splicing is under strict temporal and spatial regulation. For example, while similar patterns of splicing were found for all wild-type thoracic imaginal disks examined, these differed distinctly from the patterns observed in neural tissues. Our results suggest that individual RNAs may be associated with different biological roles, and provide molecular evidence that the Antennapedia gene is involved in multiple functions.

scholarly journals ALG-1 Influences Accurate mRNA Splicing Patterns in the Caenorhabditis elegans Intestine and Body Muscle Tissues by Modulating Splicing Factor Activities

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 931-951 ◽  
Author(s):  
Kasuen Kotagama ◽  
Anna L. Schorr ◽  
Hannah S. Steber ◽  
Marco Mangone
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Rna Splicing ◽  
Specific Gene ◽  
Splicing Factors ◽  
Tissue Specific ◽  
Link Type ◽  
Body Muscle ◽  
Mirna Targets ◽  
Mirna Pathway

MicroRNAs (miRNAs) are known to modulate gene expression, but their activity at the tissue-specific level remains largely uncharacterized. To study their contribution to tissue-specific gene expression, we developed novel tools to profile putative miRNA targets in the Caenorhabditis elegans intestine and body muscle. We validated many previously described interactions and identified ∼3500 novel targets. Many of the candidate miRNA targets curated are known to modulate the functions of their respective tissues. Within our data sets we observed a disparity in the use of miRNA-based gene regulation between the intestine and body muscle. The intestine contained significantly more putative miRNA targets than the body muscle highlighting its transcriptional complexity. We detected an unexpected enrichment of RNA-binding proteins targeted by miRNA in both tissues, with a notable abundance of RNA splicing factors. We developed in vivo genetic tools to validate and further study three RNA splicing factors identified as putative miRNA targets in our study (asd-2, hrp-2, and smu-2), and show that these factors indeed contain functional miRNA regulatory elements in their 3′UTRs that are able to repress their expression in the intestine. In addition, the alternative splicing pattern of their respective downstream targets (unc-60, unc-52, lin-10, and ret-1) is dysregulated when the miRNA pathway is disrupted. A reannotation of the transcriptome data in C. elegans strains that are deficient in the miRNA pathway from past studies supports and expands on our results. This study highlights an unexpected role for miRNAs in modulating tissue-specific gene isoforms, where post-transcriptional regulation of RNA splicing factors associates with tissue-specific alternative splicing.

scholarly journals Defective control of pre–messenger RNA splicing in human disease

2016 ◽  
Vol 212 (1) ◽  
pp. 13-27 ◽  
Author(s):  
Benoit Chabot ◽  
Lulzim Shkreta
Keyword(s):  
Alternative Splicing ◽  
Human Disease ◽  
Rna Splicing ◽  
Messenger Rna ◽  
Recent Progress ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Proteins ◽  
Regulatory Sequence ◽  
Sequence Elements

Examples of associations between human disease and defects in pre–messenger RNA splicing/alternative splicing are accumulating. Although many alterations are caused by mutations in splicing signals or regulatory sequence elements, recent studies have noted the disruptive impact of mutated generic spliceosome components and splicing regulatory proteins. This review highlights recent progress in our understanding of how the altered splicing function of RNA-binding proteins contributes to myelodysplastic syndromes, cancer, and neuropathologies.

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