scholarly journals The circadian clock shapes the Arabidopsis transcriptome by regulating alternative splicing and alternative polyadenylation

2020 ◽  
Vol 295 (22) ◽  
pp. 7608-7619 ◽  
Author(s):  
Yuchen Yang ◽  
Yun Li ◽  
Aziz Sancar ◽  
Onur Oztas
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Circadian Clock ◽  
Posttranscriptional Regulation ◽  
Environmental Changes ◽  
Intron Retention ◽  
Regulation Of Gene Expression ◽  
Alternative Polyadenylation ◽  
Genome Wide ◽  
Plant Genes

The circadian clock in plants temporally coordinates biological processes throughout the day, synchronizing gene expression with diurnal environmental changes. Circadian oscillator proteins are known to regulate the expression of clock-controlled plant genes by controlling their transcription. Here, using a high-throughput RNA-Seq approach, we examined genome-wide circadian and diurnal control of the Arabidopsis transcriptome, finding that the oscillation patterns of different transcripts of multitranscript genes can exhibit substantial differences and demonstrating that the circadian clock affects posttranscriptional regulation. In parallel, we found that two major posttranscriptional mechanisms, alternative splicing (AS; especially intron retention) and alternative polyadenylation (APA), display circadian rhythmicity resulting from oscillation in the genes involved in AS and APA. Moreover, AS-related genes exhibited rhythmic AS and APA regulation, adding another layer of complexity to circadian regulation of gene expression. We conclude that the Arabidopsis circadian clock not only controls transcription of genes but also affects their posttranscriptional regulation by influencing alternative splicing and alternative polyadenylation.

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 Alternative Splicing During the Chlamydomonasreinhardtii Cell Cycle

2020 ◽  
Vol 10 (10) ◽  
pp. 3797-3810
Author(s):  
Manishi Pandey ◽  
Gary D. Stormo ◽  
Susan K. Dutcher
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Alternative Splicing ◽  
Chlamydomonas Reinhardtii ◽  
Intron Retention ◽  
Exon Skipping ◽  
Dark Phase ◽  
Periodic Patterns ◽  
Genome Wide ◽  
Splicing Pattern

Genome-wide analysis of transcriptome data in Chlamydomonas reinhardtii shows periodic patterns in gene expression levels when cultures are grown under alternating light and dark cycles so that G1 of the cell cycle occurs in the light phase and S/M/G0 occurs during the dark phase. However, alternative splicing, a process that enables a greater protein diversity from a limited set of genes, remains largely unexplored by previous transcriptome based studies in C. reinhardtii. In this study, we used existing longitudinal RNA-seq data obtained during the light-dark cycle to investigate the changes in the alternative splicing pattern and found that 3277 genes (19.75% of 17,746 genes) undergo alternative splicing. These splicing events include Alternative 5′ (Alt 5′), Alternative 3′ (Alt 3′) and Exon skipping (ES) events that are referred as alternative site selection (ASS) events and Intron retention (IR) events. By clustering analysis, we identified a subset of events (26 ASS events and 10 IR events) that show periodic changes in the splicing pattern during the cell cycle. About two-thirds of these 36 genes either introduce a pre-termination codon (PTC) or introduce insertions or deletions into functional domains of the proteins, which implicate splicing in altering gene function. These findings suggest that alternative splicing is also regulated during the Chlamydomonas cell cycle, although not as extensively as changes in gene expression. The longitudinal changes in the alternative splicing pattern during the cell cycle captured by this study provides an important resource to investigate alternative splicing in genes of interest during the cell cycle in Chlamydomonas reinhardtii and other eukaryotes.

scholarly journals Computational modelling unravels the precise clockwork of cyanobacteria

2018 ◽  
Vol 8 (6) ◽  
pp. 20180038 ◽  
Author(s):  
Nicolas M. Schmelling ◽  
Ilka M. Axmann
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Circadian Clock ◽  
Environmental Changes ◽  
Regulation Of Gene Expression ◽  
Computational Modelling ◽  
Circadian Clocks ◽  
Fitness Advantage ◽  
Fundamental Part ◽  
Global Gene Regulation

Precisely timing the regulation of gene expression by anticipating recurring environmental changes is a fundamental part of global gene regulation. Circadian clocks are one form of this regulation, which is found in both eukaryotes and prokaryotes, providing a fitness advantage for these organisms. Whereas many different eukaryotic groups harbour circadian clocks, cyanobacteria are the only known oxygenic phototrophic prokaryotes to regulate large parts of their genes in a circadian fashion. A decade of intensive research on the mechanisms and functionality using computational and mathematical approaches in addition to the detailed biochemical and biophysical understanding make this the best understood circadian clock. Here, we summarize the findings and insights into various parts of the cyanobacterial circadian clock made by mathematical modelling. These findings have implications for eukaryotic circadian research as well as synthetic biology harnessing the power and efficiency of global gene regulation.

scholarly journals Progressive lengthening of 3′ untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development

2009 ◽  
Vol 106 (17) ◽  
pp. 7028-7033 ◽  
Author(s):  
Zhe Ji ◽  
Ju Youn Lee ◽  
Zhenhua Pan ◽  
Bingjun Jiang ◽  
Bin Tian
Keyword(s):  
Gene Expression ◽  
Embryonic Development ◽  
Posttranscriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Alternative Polyadenylation ◽  
Untranslated Regions ◽  
C2c12 Myoblast ◽  
Control Of Gene Expression ◽  
Differentiation And Proliferation

The 3′ untranslated regions (3′ UTRs) of mRNAs containcis-acting elements for posttranscriptional regulation of gene expression. Here, we report that mouse genes tend to express mRNAs with longer 3′ UTRs as embryonic development progresses. This global regulation is controlled by alternative polyadenylation and coordinates with initiation of organogenesis and aspects of embryonic development, including morphogenesis, differentiation, and proliferation. Using myogenesis of C2C12 myoblast cells as a model, we recapitulated this process in vitro and found that 3′ UTR lengthening is likely caused by weakening of mRNA polyadenylation activity. Because alternative 3′ UTR sequences are typically longer and have higher AU content than constitutive ones, our results suggest that lengthening of 3′ UTR can significantly augment posttranscriptional control of gene expression during embryonic development, such as microRNA-mediated regulation.

scholarly journals Gene Expression and Alternative Splicing Dynamics Are Perturbed in Head Transcriptomes of Heterospecifically Mated Females

2021 ◽  
Author(s):  
Fernando Diaz ◽  
Carson Allan ◽  
Therese Markow ◽  
Jeremy Bono ◽  
Luciano Matzkin
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Reproductive Tract ◽  
Seminal Fluid ◽  
Intron Retention ◽  
Transcriptional Responses ◽  
Seminal Fluid Proteins ◽  
Genome Wide ◽  
Amino Acid Balance ◽  
Postmating Behavior

Abstract Background Despite the growing interest in the female side of copulatory interactions, the roles played by alternative splicing mechanisms of pre-RNA and the epistatic effects of these interactions on tissues outside of the reproductive tract have remained largely unknown. Here we addressed these questions in the context of con- vs heterospecific matings between Drosophila mojavensis and its sister species, D. arizonae. We analyzed transcriptional responses in female heads using an integrated investigation of genome-wide patterns of gene expression, including differential expression (DE), alternative splicing (AS) and intron retention (IR). Results Our results indicated that early transcriptional responses were largely congruent between con- and heterospecific matings but are substantially perturbed over time. Conspecific matings induced functional pathways related to amino acid balance previously associated with the brain’s physiology and female postmating behavior. Heterospecific matings often fail to activate regulation of some of these genes and induce expression of additional genes when compared with those of conspecifically-mated females. These results are consistent for all transcriptional mechanisms with some distinctions: DE genes were mostly linked to pathways of proteolysis and nutrient homeostasis, while AS genes are more related to photoreception and muscle assembly pathways. Conclusions IR seem to be an important mechanism of DE regulation during the female postmating response. While AS genes evolve at slower evolutionary rates than the genome background, DE genes evolve at much higher rates, similar or even higher than those of seminal fluid proteins, which unveil their potential role for reproductive barriers and the extent of sexual conflict.

scholarly journals The fitness cost of mis-splicing is the main determinant of alternative splicing patterns

2017 ◽  
Author(s):  
Baptiste Saudemont ◽  
Alexandra Popa ◽  
Joanna L. Parmley ◽  
Vincent Rocher ◽  
Corinne Blugeon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Splice Variants ◽  
Intron Retention ◽  
Relative Proportion ◽  
Regulation Of Gene Expression ◽  
Fitness Cost ◽  
Expression Level ◽  
Unicellular Eukaryote ◽  
Eukaryotic Genes

ABSTRACTMost eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of functional protein variants or to the regulation of gene expression, notably via nonsense-mediated mRNA decay (NMD). However, a fraction of splice variants might correspond to spurious transcripts, and the question of the relative proportion of splicing errors vs. functional splice variants remains highly debated. We propose here a test to quantify the fraction of AS events corresponding to errors. This test is based on the fact that the fitness cost of splicing errors increases with the number of introns in a gene and with expression level. We first analyzed the transcriptome of the intron-rich unicellular eukaryote Paramecium tetraurelia. We show that both in normal and in NMD-deficient cells, AS rates (intron retention, alternative splice site usage or cryptic intron splicing) strongly decrease with increasing expression level and with increasing number of introns. This relationship is observed both for AS events that are detectable by NMD or not, which invalidates the hypothesis of a possible link with the regulation of gene expression. Our results indicate that in genes with a median expression level, 92%-98% of observed splice variants correspond to errors. Interestingly, we observed the same patterns in human transcriptomes. These results are consistent with the mutation-selection-drift theory, which predicts that genes under weaker selective pressure should accumulate more maladaptive substitutions, and therefore should be more prone to errors of gene expression.

scholarly journals Genome-Wide Differences in Gene Expression and Alternative Splicing in Developing Embryo and Endosperm, and Between F1 Hybrids and Their Parental Pure Lines in Sorghum

2021 ◽  
Author(s):  
Meishan Zhang ◽  
Ning Li ◽  
Weiguang Yang ◽  
Bao Liu
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Pure Line ◽  
F1 Hybrids ◽  
Plant Growth And Development ◽  
Genome Wide ◽  
Pure Lines ◽  
Genome Wide Gene Expression

Abstract Differential regulation of gene expression and alternative splicing (AS) are major molecular mechanisms dictating plant growth and development, as well as underpinning heterosis in F1 hybrids. Here, using deep RNA-sequencing we analyzed differences in genome-wide gene expression and AS between developing embryo and endosperm, and between F1 hybrids and their pure-line parents in sorghum. We uncover dramatic differences in both gene expression and AS between embryo and endosperm with respect to gene features and functions, which are consistent with the fundamentally different biological roles of the two tissues. Accordingly, F1 hybrids showed substantial and multifaceted differences in gene expression and AS compared with their pure-line parents, again with clear tissue specificities including extents of difference, genes involved and functional enrichments. Our results provide useful transcriptome resources as well as novel insights for further elucidation of seed yield heterosis in sorghum and related crops.

scholarly journals Ctcf Haploinsufficiency Mediates Intron Retention in A Tissue-specific Manner

2019 ◽  
Author(s):  
Adel B Alharbi ◽  
Ulf Schmitz ◽  
Amy D Marshall ◽  
Darya Vanichkina ◽  
Rajini Nagarajah ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intron Retention ◽  
Regulation Of Gene Expression ◽  
Splicing Factors ◽  
Tissue Specific ◽  
Genome Wide ◽  
Liver And Kidney ◽  
Specific Regulation ◽  
Dose Dependent

AbstractCTCF is a master regulator of gene transcription and chromatin organization with occupancy at thousands of DNA target sites. CTCF is essential for embryonic development and somatic cell viability and has been characterized as a haploinsufficient tumor suppressor. Increasing evidence demonstrates CTCF as a key player in several alternative splicing (AS) regulatory mechanisms, including transcription elongation, regulation of splicing factors, and epigenetic regulation. However, the genome-wide impact of Ctcf dosage on AS has not been investigated. We examined the effect of Ctcf haploinsufficiency on gene expression and AS in multiple tissues from Ctcf hemizygous (Ctcf+/-) mice. Distinct tissue-specific differences in gene expression and AS were observed in Ctcf+/- mice compared to wildtype mice. We observed a surprisingly large number of increased intron retention (IR) events in Ctcf+/- liver and kidney, specifically in genes associated with cytoskeletal organization, splicing and metabolism. This study provides further evidence for Ctcf dose-dependent and tissue-specific regulation of gene expression and AS. Our data provide a strong foundation for elucidating the mechanistic role of CTCF in AS regulation and its biological consequences.

scholarly journals STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lionel Condé ◽  
Yulemi Gonzalez Quesada ◽  
Florence Bonnet-Magnaval ◽  
Rémy Beaujois ◽  
Luc DesGroseillers
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Steady State ◽  
Posttranscriptional Regulation ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Cycle Progression

AbstractBackgroundStaufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from theSTAU2gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation.ResultsCRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism.ConclusionsThese results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.

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