Regulation of Gene Expression by Coupling of Alternative Splicing and NMD

2006 ◽  
pp. 193-214
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Regulation Of Gene Expression

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 Cellular stressors may alter islet hormone cell proportions by moderation of alternative splicing patterns

2019 ◽  
Vol 28 (16) ◽  
pp. 2763-2774 ◽  
Author(s):  
Nicola Jeffery ◽  
Sarah Richardson ◽  
David Chambers ◽  
Noel G Morgan ◽  
Lorna W Harries
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Regulation Of Gene Expression ◽  
Splicing Factor ◽  
Splicing Regulation ◽  
Messenger Ribonucleic Acid ◽  
Splicing Patterns ◽  
Cellular Stressors

Abstract Changes to islet cell identity in response to type 2 diabetes (T2D) have been reported in rodent models, but are less well characterized in humans. We assessed the effects of aspects of the diabetic microenvironment on hormone staining, total gene expression, splicing regulation and the alternative splicing patterns of key genes in EndoC-βH1 human beta cells. Genes encoding islet hormones [somatostatin (SST), insulin (INS), Glucagon (GCG)], differentiation markers [Forkhead box O1 (FOXO1), Paired box 6, SRY box 9, NK6 Homeobox 1, NK6 Homeobox 2] and cell stress markers (DNA damage inducible transcript 3, FOXO1) were dysregulated in stressed EndoC-βH1 cells, as were some serine arginine rich splicing factor splicing activator and heterogeneous ribonucleoprotein particle inhibitor genes. Whole transcriptome analysis of primary T2D islets and matched controls demonstrated dysregulated splicing for ~25% of splicing events, of which genes themselves involved in messenger ribonucleic acid processing and regulation of gene expression comprised the largest group. Approximately 5% of EndoC-βH1 cells exposed to these factors gained SST positivity in vitro. An increased area of SST staining was also observed ex vivo in pancreas sections recovered at autopsy from donors with type 1 diabetes (T1D) or T2D (9.3% for T1D and 3% for T2D, respectively compared with 1% in controls). Removal of the stressful stimulus or treatment with the AKT Serine/Threonine kinase inhibitor SH-6 restored splicing factor expression and reversed both hormone staining effects and patterns of gene expression. This suggests that reversible changes in hormone expression may occur during exposure to diabetomimetic cellular stressors, which may be mediated by changes in splicing regulation.

scholarly journals Differential fates of introns in gene expression due to global alternative splicing

2021 ◽  
Author(s):  
Anjani Kumari ◽  
Saam Sedehizadeh ◽  
John David Brook ◽  
Piotr Kozlowski ◽  
Marzena Wojciechowska
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Neuromuscular Disorders ◽  
Regulation Of Gene Expression ◽  
Protein Isoforms ◽  
Circular Rnas ◽  
Surveillance Systems ◽  
Myotonic Dystrophy Type 2 ◽  
New Vision ◽  
And Function

AbstractThe discovery of introns over four decades ago revealed a new vision of genes and their interrupted arrangement. Throughout the years, it has appeared that introns play essential roles in the regulation of gene expression. Unique processing of excised introns through the formation of lariats suggests a widespread role for these molecules in the structure and function of cells. In addition to rapid destruction, these lariats may linger on in the nucleus or may even be exported to the cytoplasm, where they remain stable circular RNAs (circRNAs). Alternative splicing (AS) is a source of diversity in mature transcripts harboring retained introns (RI-mRNAs). Such RNAs may contain one or more entire retained intron(s) (RIs), but they may also have intron fragments resulting from sequential excision of smaller subfragments via recursive splicing (RS), which is characteristic of long introns. There are many potential fates of RI-mRNAs, including their downregulation via nuclear and cytoplasmic surveillance systems and the generation of new protein isoforms with potentially different functions. Various reports have linked the presence of such unprocessed transcripts in mammals to important roles in normal development and in disease-related conditions. In certain human neurological-neuromuscular disorders, including myotonic dystrophy type 2 (DM2), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and Duchenne muscular dystrophy (DMD), peculiar processing of long introns has been identified and is associated with their pathogenic effects. In this review, we discuss different mechanisms involved in the processing of introns during AS and the functions of these large sections of the genome in our biology.

scholarly journals Comprehensive Identification and Alternative Splicing of Microexons in Drosophila

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting-Lin Pang ◽  
Zhan Ding ◽  
Shao-Bo Liang ◽  
Liang Li ◽  
Bei Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Sex Determination ◽  
Rna Splicing ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Pathway Gene ◽  
Mrna Transcripts ◽  
Bioinformatic Tool ◽  
Alternatively Spliced

Interrupted exons in the pre-mRNA transcripts are ligated together through RNA splicing, which plays a critical role in the regulation of gene expression. Exons with a length ≤ 30 nt are defined as microexons that are unique in identification. However, microexons, especially those shorter than 8 nt, have not been well studied in many organisms due to difficulties in mapping short segments from sequencing reads. Here, we analyzed mRNA-seq data from a variety of Drosophila samples with a newly developed bioinformatic tool, ce-TopHat. In addition to the Flybase annotated, 465 new microexons were identified. Differentially alternatively spliced (AS) microexons were investigated between the Drosophila tissues (head, body, and gonad) and genders. Most of the AS microexons were found in the head and two AS microexons were identified in the sex-determination pathway gene fruitless.

scholarly journals Phosphorylation-Mediated Regulation of Alternative Splicing in Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Chiara Naro ◽  
Claudio Sette
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Posttranslational Modifications ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Splice Variants ◽  
Single Gene ◽  
Regulation Of Gene Expression ◽  
Eukaryotic Cells ◽  
Macromolecular Complex

Alternative splicing (AS) is one of the key processes involved in the regulation of gene expression in eukaryotic cells. AS catalyzes the removal of intronic sequences and the joining of selected exons, thus ensuring the correct processing of the primary transcript into the mature mRNA. The combinatorial nature of AS allows a great expansion of the genome coding potential, as multiple splice-variants encoding for different proteins may arise from a single gene. Splicing is mediated by a large macromolecular complex, the spliceosome, whose activity needs a fine regulation exerted bycis-acting RNA sequence elements andtrans-acting RNA binding proteins (RBP). The activity of both core spliceosomal components and accessory splicing factors is modulated by their reversible phosphorylation. The kinases and phosphatases involved in these posttranslational modifications significantly contribute to AS regulation and to its integration in the complex regulative network that controls gene expression in eukaryotic cells. Herein, we will review the major canonical and noncanonical splicing factor kinases and phosphatases, focusing on those whose activity has been implicated in the aberrant splicing events that characterize neoplastic transformation.

DDX21 interacts with nuclear AGO2 and regulates the alternative splicing of SMN2

2020 ◽  
Vol 85 (2) ◽  
pp. 272-279
Author(s):  
Mengting Gong ◽  
Xi Zhang ◽  
Yaru Wang ◽  
Guiyan Mao ◽  
Yangqi Ou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Gene Silencing ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Dependent Manner ◽  
Indirect Interaction ◽  
Multiple Gene ◽  
Multiple Gene Silencing

ABSTRACT AGO2 is the only member of mammalian Ago protein family that possesses the catalytic activity and plays a central role in gene silencing. Recently researches reported that multiple gene silencing factors, including AGO2, function in the nuclei. The molecular mechanisms of the gene silencing factors functioning in nuclei are conducive to comprehend the roles of gene silencing in pretranslational regulation of gene expression. Here, we report that AGO2 interacts with DDX21 indirectly in an RNA-dependent manner by Co-IP and GST-Pulldown assays and the 2 proteins present nuclei foci in the immunofluorescence experiments. We found that DDX21 up-regulated the protein level of AGO2 and participated in target gene, SNM2, alternative splicing involved in AGO2 by the indirect interaction with AGO2, which produced different transcripts of SMN2 in discrepant expression level. This study laid important experiment foundation for the further analysis of the nuclear functions of gene silencing components.

scholarly journals Identification and characterisation of splicing regulators in Toxoplasma gondii

2021 ◽  
Author(s):  
V Vern Lee ◽  
Simona Seizova ◽  
Paul McMillan ◽  
Emma McHugh ◽  
Chris Tonkin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Toxoplasma Gondii ◽  
Regulation Of Gene Expression ◽  
Transcript Abundance ◽  
Sr Proteins ◽  
Splicing Factors ◽  
Simple Relationship ◽  
Nuclear Speckles ◽  
Genetic Ablation

The splicing of mRNA constitutes a major source of co- and post-transcriptional regulation in metazoans. In particular, members of the serine/arginine (SR) protein family are essential splicing factors that are implicated in the regulation of gene expression and RNA metabolism. However, very little is known about these proteins in apicomplexans, a phylum that includes some of the most important global parasites. In this study, we investigated the suite of three uncharacterised SR proteins in Toxoplasma gondii and show that all three are found localised to nuclear speckles. We show, by genetic ablation, that TgSR1 is particularly important for T. gondii growth. Using RNA-seq, we also characterised the global gene expression and splicing regulation of these proteins. We find that the SR proteins regulate several types of alternative splicing of distinct but overlapping subsets of transcripts, as well as impacting transcript abundance. Most of the alternative splicing events are non-productive intron retention events that do not appear to affect transcript abundance. The splicing sites of the impacted transcripts are enriched in characteristic SR binding motifs. We also identified and conditionally knocked down two putative kinases of SR proteins. The kinases are localised to nuclear speckles and are essential to parasite survival. Their perturbation resulted in widespread changes to splicing, but the affected transcripts did not mirror the patterns seen in knockouts of individual SRs, suggesting an absence of a simple relationship between SRs and these putative kinase regulators. Overall, this study reveals a complex system of splicing factors and kinases that post-transcriptionally regulate gene expression in T. gondii.

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