scholarly journals The U1 snRNP subunit LUC7 controls plant development and stress response through alternative splicing regulation

2017 ◽  
Author(s):  
Marcella de Francisco Amorim ◽  
Eva-Maria Willing ◽  
Anchilie G. Francisco-Mangilet ◽  
Irina Droste-Borel ◽  
Boris Maček ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Plant Development ◽  
Nuclear Export ◽  
Macromolecular Complex ◽  
Splicing Regulation ◽  
Dependent Manner ◽  
Accessory Factor ◽  
U1 Snrnp ◽  
Member Gene ◽  
Rna Immunoprecipitation

AbstractIntrons are removed by the spliceosome, a large macromolecular complex composed of five ribonucleoprotein subcomplexes (U snRNP). The U1 snRNP, which binds to 5’ splice sites, plays an essential role in early steps of the splicing reaction. Here, we show that Arabidopsis LUC7 proteins, which are encoded by a three-member gene family in Arabidopsis, are important for plant development and stress resistance. We show that LUC7 are U1 snRNP accessory proteins by RNA immunoprecipitation experiments and LUC7 protein complex purifications. Transcriptome analyses revealed that LUC7 proteins are not only important for constitutive splicing, but also affects hundreds of alternative splicing events. Interestingly, LUC7 proteins specifically promote splicing of a subset of terminal introns. Splicing of LUC7-dependent introns is a prerequisite for nuclear export and some splicing events are modulated by stress in a LUC7-dependent manner. Taken together our results highlight the importance of the U1 snRNP component LUC7 in splicing regulation and suggest a previously unrecognized role of a U1 snRNP accessory factor in terminal intron splicing.

scholarly journals The U1 snRNP Subunit LUC7 Modulates Plant Development and Stress Responses via Regulation of Alternative Splicing

2018 ◽  
Vol 30 (11) ◽  
pp. 2838-2854 ◽  
Author(s):  
Marcella de Francisco Amorim ◽  
Eva-Maria Willing ◽  
Emese X. Szabo ◽  
Anchilie G. Francisco-Mangilet ◽  
Irina Droste-Borel ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Plant Development ◽  
Stress Responses ◽  
U1 Snrnp

scholarly journals The RNA-binding protein Staufen1 is increased in DM1 skeletal muscle and promotes alternative pre-mRNA splicing

2012 ◽  
Vol 196 (6) ◽  
pp. 699-712 ◽  
Author(s):  
Aymeric Ravel-Chapuis ◽  
Guy Bélanger ◽  
Ramesh S. Yadava ◽  
Mani S. Mahadevan ◽  
Luc DesGroseillers ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Alternative Splicing ◽  
Nuclear Export ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Splicing Regulation ◽  
Ribonucleic Acids ◽  
Dystrophia Myotonica Protein Kinase

In myotonic dystrophy type 1 (DM1), dystrophia myotonica protein kinase messenger ribonucleic acids (RNAs; mRNAs) with expanded CUG repeats (CUGexp) aggregate in the nucleus and become toxic to cells by sequestering and/or misregulating RNA-binding proteins, resulting in aberrant alternative splicing. In this paper, we find that the RNA-binding protein Staufen1 is markedly and specifically increased in skeletal muscle from DM1 mouse models and patients. We show that Staufen1 interacts with mutant CUGexp mRNAs and promotes their nuclear export and translation. This effect is critically dependent on the third double-stranded RNA–binding domain of Staufen1 and shuttling of Staufen1 into the nucleus via its nuclear localization signal. Moreover, we uncover a new role of Staufen1 in splicing regulation. Overexpression of Staufen1 rescues alternative splicing of two key pre-mRNAs known to be aberrantly spliced in DM1, suggesting its increased expression represents an adaptive response to the pathology. Altogether, our results unravel a novel function for Staufen1 in splicing regulation and indicate that it may positively modulate the complex DM1 phenotype, thereby revealing its potential as a therapeutic target.

scholarly journals Novel roles of U1 snRNP in alternative splicing regulation

RNA Biology ◽  
2010 ◽  
Vol 7 (4) ◽  
pp. 412-419 ◽  
Author(s):  
Emanuele Buratti ◽  
Diana Baralle
Keyword(s):  
Alternative Splicing ◽  
Splicing Regulation ◽  
U1 Snrnp

scholarly journals Intragenic recruitment of NF-κB drives alternative splicing modifications upon activation by the viral oncogene TAX of HTLV-1

2019 ◽  
Author(s):  
Lamya Ben Ameur ◽  
Morgan Thenoz ◽  
Guillaume Giraud ◽  
Emmanuel Combe ◽  
Jean-Baptiste Claude ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Splicing ◽  
Major Part ◽  
Splicing Regulation ◽  
Dependent Manner ◽  
Gene Promoters ◽  
Helicase Activity ◽  
Viral Oncogene ◽  
Oncogenic Pathways ◽  
Splicing Regulator

SummaryThe chronic NF-κB activation in inflammation and cancer has long been linked to persistent activation of NF-κB responsive gene promoters. However, NF-κB factors such as RELA also massively bind to gene bodies. Here, we demonstrate that the recruitment of RELA to intragenic regions regulates alternative splicing upon activation of NF-κB by the viral oncogene TAX of HTLV-1. Integrative analysis of RNA splicing and chromatin occupancy, combined with chromatin tethering assays, demonstrate that DNA-bound RELA interacts with and recruits the splicing regulator DDX17 in a NF-kB activation-dependent manner, leading to alternative splicing of target exons thanks to DDX17 RNA helicase activity. This NF-kB/DDX17 axis accounts for a major part of the TAX-induced alternative splicing landscape that mainly affects genes involved in oncogenic pathways. Collectively, our results demonstrate a physical and direct involvement of NF-κB in alternative splicing regulation, which significantly revisits our knowledge of HTLV-1 pathogenesis and other NF-κB-related diseases.

scholarly journals Mex67p of Schizosaccharomyces pombeInteracts with Rae1p in Mediating mRNA Export

2000 ◽  
Vol 20 (23) ◽  
pp. 8767-8782 ◽  
Author(s):  
Jin Ho Yoon ◽  
Dona C. Love ◽  
Anjan Guhathakurta ◽  
John A. Hanover ◽  
Ravi Dhar
Keyword(s):  
Nuclear Export ◽  
Rna Binding ◽  
Fluorescent Protein ◽  
Synthetic Lethality ◽  
Sequence Similarity ◽  
Mrna Export ◽  
Nuclear Periphery ◽  
Nuclear Pore ◽  
Multicopy Suppressor ◽  
Accessory Factor

ABSTRACT We identified the Schizosaccharomyces pombe mex67 gene (spmex67) as a multicopy suppressor of rae1-167 nup184-1 synthetic lethality and the rae1-167 tsmutation. spMex67p, a 596-amino-acid-long protein, has considerable sequence similarity to the Saccharomyces cerevisiae Mex67p (scMex67p) and human Tap. In contrast toscMEX67, spmex67 is essential for neither growth nor nuclear export of mRNA. However, an spmex67 null mutation (Δmex67) is synthetically lethal with therae1-167 mutation and accumulates poly(A)+ RNA in the nucleus. We identified a central region (149 to 505 amino acids) within spMex67p that associates with a complex containing Rae1p that complements growth and mRNA export defects of therae1-167 Δmex67 synthetic lethality. This region is devoid of RNA-binding, N-terminal nuclear localization, and the C-terminal nuclear pore complex-targeting regions. The (149–505)-green fluorescent protein (GFP) fusion is found diffused throughout the cell. Overexpression of spMex67p inhibits growth and mRNA export and results in the redistribution of the diffused localization of the (149–505)-GFP fusion to the nucleus and the nuclear periphery. These results suggest that spMex67p competes for essential mRNA export factor(s). Finally, we propose that the 149–505 region of spMex67p could act as an accessory factor in Rae1p-dependent transport and that spMex67p participates at various common steps with Rae1p export complexes in promoting the export of mRNA.

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 Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation

2015 ◽  
Vol 35 (10) ◽  
pp. 1700-1711 ◽  
Author(s):  
Fenfang Chen ◽  
Xia Lin ◽  
Pinglong Xu ◽  
Zhengmao Zhang ◽  
Yanzhen Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Mesenchymal Stem Cell ◽  
Nuclear Export ◽  
Stem Cell Differentiation ◽  
Bmp Signaling ◽  
Dependent Manner ◽  
Mesenchymal Stem Cell Differentiation

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.

scholarly journals Nova Regulates GABAA Receptor γ2 Alternative Splicing via a Distal Downstream UCAU-Rich Intronic Splicing Enhancer

2003 ◽  
Vol 23 (13) ◽  
pp. 4687-4700 ◽  
Author(s):  
B. Kate Dredge ◽  
Robert B. Darnell
Keyword(s):  
Alternative Splicing ◽  
Rna Binding ◽  
Splice Acceptor Site ◽  
Acceptor Site ◽  
Splicing Regulation ◽  
Globin Genes ◽  
Enhancer Element ◽  
Intronic Splicing Enhancer ◽  
Splicing Enhancer

ABSTRACT Nova is a neuron-specific RNA binding protein targeted in patients with the autoimmune disorder paraneoplastic opsoclonus-myoclonus ataxia, which is characterized by failure of inhibition of brainstem and spinal motor systems. Here, we have biochemically confirmed the observation that splicing regulation of the inhibitory GABAA receptor γ2 (GABAARγ2) subunit pre-mRNA exon E9 is disrupted in mice lacking Nova-1. To elucidate the mechanism by which Nova-1 regulates GABAARγ2 alternative splicing, we systematically screened minigenes derived from the GABAARγ2 and human β-globin genes for their ability to support Nova-dependent splicing in transient transfection assays. These studies demonstrate that Nova-1 acts directly on GABAARγ2 pre-mRNA to regulate E9 splicing and identify an intronic region that is necessary and sufficient for Nova-dependent enhancement of exon inclusion, which we term the NISE (Nova-dependent intronic splicing enhancer) element. The NISE element (located 80 nucleotides upstream of the splice acceptor site of the downstream exon E10) is composed of repeats of the sequence YCAY, consistent with previous studies of the mechanism by which Nova binds RNA. Mutation of these repeats abolishes binding of Nova-1 to the RNA in vitro and Nova-dependent splicing regulation in vivo. These data provide a molecular basis for understanding Nova regulation of GABAARγ2 alternative splicing and suggest that general dysregulation of Nova's splicing enhancer function may underlie the neurologic defects seen in Nova's absence.

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