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exon junction complex

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https://www.readbyqxmd.com/read/28539927/a-comprehensive-analysis-of-alternative-splicing-in-paleopolyploid-maize
#1
Wenbin Mei, Sanzhen Liu, James C Schnable, Cheng-Ting Yeh, Nathan M Springer, Patrick S Schnable, William B Barbazuk
Identifying and characterizing alternative splicing (AS) enables our understanding of the biological role of transcript isoform diversity. This study describes the use of publicly available RNA-Seq data to identify and characterize the global diversity of AS isoforms in maize using the inbred lines B73 and Mo17, and a related species, sorghum. Identification and characterization of AS within maize tissues revealed that genes expressed in seed exhibit the largest differential AS relative to other tissues examined...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28539829/multifaceted-regulation-of-gene-expression-by-the-apoptosis-and-splicing-associated-protein-complex-and-its-components
#2
REVIEW
Bhagyashree Deka, Kusum Kumari Singh
The differential deposition of RNA-binding proteins (RBPs) on pre-mRNA mediates the processes of gene expression. One of the complexes containing RBPs that play a crucial part in RNA metabolism is the apoptosis-and splicing-associated protein (ASAP) complex. In this review, we present a summary of the structure of ASAP complex and its localization. Also, we discuss the findings by different groups on various functions of the subunits of the ASAP complex in RNA metabolism. The subunits of the ASAP complex are RNPS1, Acinus and SAP18...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28502770/an-atomic-structure-of-the-human-spliceosome
#3
Xiaofeng Zhang, Chuangye Yan, Jing Hang, Lorenzo I Finci, Jianlin Lei, Yigong Shi
Mechanistic understanding of pre-mRNA splicing requires detailed structural information on various states of the spliceosome. Here we report the cryo electron microscopy (cryo-EM) structure of the human spliceosome just before exon ligation (the C(∗) complex) at an average resolution of 3.76 Å. The splicing factor Prp17 stabilizes the active site conformation. The step II factor Slu7 adopts an extended conformation, binds Prp8 and Cwc22, and is poised for selection of the 3'-splice site. Remarkably, the intron lariat traverses through a positively charged central channel of RBM22; this unusual organization suggests mechanisms of intron recruitment, confinement, and release...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28440616/discovery-and-characterization-of-a-eukaryotic-initiation-factor-4a-3-selective-inhibitor-that-suppresses-nonsense-mediated-mrna-decay
#4
Misa Iwatani-Yoshihara, Masahiro Ito, Yoshihiro Ishibashi, Hideyuki Oki, Toshio Tanaka, Daisuke Morishita, Takashi Ito, Hiromichi Kimura, Yasuhiro Imaeda, Samuel Aparicio, Atsushi Nakanishi, Tomohiro Kawamoto
Eukaryotic initiation factor 4A-3 (eIF4A3) is an Asp-Glu-Ala-Asp (DEAD) box-family adenosine triphosphate (ATP)-dependent RNA helicase. Subtypes eIF4A1 and eIF4A2 are required for translation initiation, but eIF4A3 participates in the exon junction complex (EJC) and functions in RNA metabolism including nonsense-mediated RNA decay (NMD). No small molecules for NMD inhibition via selective inhibition of eIF4A3 have been discovered. Here, we identified allosteric eIF4A3 inhibitors from a high-throughput screening campaign...
May 10, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28404883/mir-29a-regulates-the-proliferation-and-differentiation-of-retinal-progenitors-by-targeting-rbm8a
#5
Yi Zhang, Bingqiao Shen, Dandan Zhang, Yuyao Wang, Zhimin Tang, Ni Ni, Xiaoliang Jin, Min Luo, Hao Sun, Ping Gu
During development, tight regulation of the expansion of retinal progenitor cells (RPCs) and their differentiation into neuronal and glial cells is important for retinal formation and function. Our study demonstrated that microRNA (miR)-29a modulated the proliferation and differentiation of RPCs by suppressing RBM8A (one of the factors in the exon junction complex). Particularly, overexpression of miR-29a reduced RPC proliferation but accelerated RPC differentiation. By contrast, reduction of endogenous miR-29a elicited the opposite effects...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402567/nonsense-mediated-mrna-decay-in-tetrahymena-is-ejc-independent-and-requires-a-protozoa-specific-nuclease
#6
Miao Tian, Wentao Yang, Jing Zhang, Huai Dang, Xingyi Lu, Chengjie Fu, Wei Miao
Nonsense-mediated mRNA decay (NMD) is essential for removing premature termination codon-containing transcripts from cells. Studying the NMD pathway in model organisms can help to elucidate the NMD mechanism in humans and improve our understanding of how this biologically important process has evolved. Ciliates are among the earliest branching eukaryotes; their NMD mechanism is poorly understood and may be primordial. We demonstrate that highly conserved Upf proteins (Upf1a, Upf2 and Upf3) are involved in the NMD pathway of the ciliate, Tetrahymena thermophila...
April 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28400409/drosha-targets-its-own-transcript-to-modulate-alternative-splicing
#7
Dooyoung Lee, Jin-Wu Nam, Chanseok Shin
The nuclear RNase III enzyme DROSHA interacts with its cofactor DGCR8 to form the Microprocessor complex, which initiates microRNA (miRNA) maturation by cleaving hairpin structures embedded in primary transcripts. Apart from its central role in the biogenesis of miRNAs, DROSHA is also known to recognize and cleave miRNA-like hairpins in a subset of transcripts without apparent small RNA production. Here, we report that the human DROSHA transcript is one such non-canonical target of DROSHA. Mammalian DROSHA genes have evolved a conserved hairpin structure spanning a specific exon-intron junction, which serves as a substrate for the Microprocessor in human cells but not in murine cells...
April 11, 2017: RNA
https://www.readbyqxmd.com/read/28393127/novel-junctophilin-2-mutation-a405s-is-associated-with-basal-septal-hypertrophy-and-diastolic-dysfunction
#8
Ann P Quick, Andrew P Landstrom, Qiongling Wang, David L Beavers, Julia O Reynolds, Giselle Barreto-Torres, Viet Tran, Jordan Showell, Leonne E Philippen, Shaine A Morris, Darlene Skapura, J Martijn Bos, Steen E Pedersen, Robia G Pautler, Michael J Ackerman, Xander H T Wehrens
BACKGROUND: Hypertrophic cardiomyopathy (HCM), defined as asymmetric left ventricular hypertrophy, is a leading cause of cardiac death in the young. Perturbations in calcium (Ca(2+)) handling proteins have been implicated in the pathogenesis of HCM. JPH2-encoded junctophilin 2 is a major component of the junctional membrane complex, the subcellular microdomain involved in excitation-contraction coupling. We hypothesized that a novel JPH2 mutation identified in patients with HCM is causally linked to HCM, and alters intracellular Ca(2+) signaling in a pro-hypertrophic manner...
February 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28361991/y14-governs-p53-expression-and-modulates-dna-damage-sensitivity
#9
Chia-Chen Lu, Chi-Chieh Lee, Ching-Tzu Tseng, Woan-Yuh Tarn
Y14 is a core component of the exon junction complex (EJC), while it also exerts cellular functions independent of the EJC. Depletion of Y14 causes G2/M arrest, DNA damage and apoptosis. Here we show that knockdown of Y14 induces the expression of an alternative spliced isoform of p53, namely p53β, in human cells. Y14, in the context of the EJC, inhibited aberrant exon inclusion during the splicing of p53 pre-mRNA, and thus prevent p53β expression. The anti-cancer agent camptothecin specifically suppressed p53β induction...
March 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28358513/discovery-of-novel-1-4-diacylpiperazines-as-selective-and-cell-active-eif4a3-inhibitors
#10
Masahiro Ito, Toshio Tanaka, Douglas R Cary, Misa Iwatani-Yoshihara, Yusuke Kamada, Tomohiro Kawamoto, Samuel Aparicio, Atsushi Nakanishi, Yasuhiro Imaeda
Eukaryotic initiation factor 4A3 (eIF4A3), a member of the DEAD-box RNA helicase family, is one of the core components of the exon junction complex (EJC). The EJC is known to be involved in a variety of RNA metabolic processes typified by nonsense-mediated RNA decay (NMD). In order to identify molecular probes to investigate the functions and therapeutic relevance of eIF4A3, a search for selective eIF4A3 inhibitors was conducted. Through the chemical optimization of 1,4-diacylpiperazine derivatives identified via high-throughput screening (HTS), we discovered the first reported selective eIF4A3 inhibitor 53a exhibiting cellular NMD inhibitory activity...
April 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28283335/discovery-of-selective-atp-competitive-eif4a3-inhibitors
#11
Masahiro Ito, Misa Iwatani, Yusuke Kamada, Satoshi Sogabe, Shoichi Nakao, Toshio Tanaka, Tomohiro Kawamoto, Samuel Aparicio, Atsushi Nakanishi, Yasuhiro Imaeda
Eukaryotic initiation factor 4A3 (eIF4A3), an ATP-dependent RNA helicase, is a core component of exon junction complex (EJC). EJC has a variety of roles in RNA metabolism such as translation, surveillance, and localization of spliced RNA. It is worthwhile to identify selective eIF4A3 inhibitors with a view to investigating the functions of eIF4A3 and EJC further to clarify the roles of the ATPase and helicase activities in cells. Our chemical optimization of hit compound 2 culminated in the discovery of ATP-competitive eIF4A3 inhibitor 18 with submicromolar ATPase inhibitory activity and excellent selectivity over other helicases...
February 20, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28273136/dux4-induced-dsrna-and-myc-mrna-stabilization-activate-apoptotic-pathways-in-human-cell-models-of-facioscapulohumeral-dystrophy
#12
Sean C Shadle, Jun Wen Zhong, Amy E Campbell, Melissa L Conerly, Sujatha Jagannathan, Chao-Jen Wong, Timothy D Morello, Silvère M van der Maarel, Stephen J Tapscott
Facioscapulohumeral dystrophy (FSHD) is caused by the mis-expression of DUX4 in skeletal muscle cells. DUX4 is a transcription factor that activates genes normally associated with stem cell biology and its mis-expression in FSHD cells results in apoptosis. To identify genes and pathways necessary for DUX4-mediated apoptosis, we performed an siRNA screen in an RD rhabdomyosarcoma cell line with an inducible DUX4 transgene. Our screen identified components of the MYC-mediated apoptotic pathway and the double-stranded RNA (dsRNA) innate immune response pathway as mediators of DUX4-induced apoptosis...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28192756/scn1a-clinical-spectrum-includes-the-self-limited-focal-epilepsies-of-childhood
#13
Sara Kivity, Karen L Oliver, Zaid Afawi, John A Damiano, Todor Arsov, Melanie Bahlo, Samuel F Berkovic
INTRODUCTION: Amongst autosomal dominant genetic epilepsy with febrile seizures plus (GEFS+) families, SCN1A variants are the most common genetic cause. Initially regarded as a generalized form of epilepsy, the GEFS+ spectrum is now known to include some focal epilepsies, but it is generally not conceptualized as extending to the self-limited focal epilepsies of childhood, such as Panayiotopoulos syndrome. There are, however, three reports of SCN1A variants in Panayiotopoulos syndrome...
March 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28166730/transcriptome-analysis-reveals-the-complexity-of-alternative-splicing-regulation-in-the-fungus-verticillium-dahliae
#14
Lirong Jin, Guanglin Li, Dazhao Yu, Wei Huang, Chao Cheng, Shengjie Liao, Qijia Wu, Yi Zhang
BACKGROUND: Alternative splicing (AS) regulation is extensive and shapes the functional complexity of higher organisms. However, the contribution of alternative splicing to fungal biology is not well studied. RESULTS: This study provides sequences of the transcriptomes of the plant wilt pathogen Verticillium dahliae, using two different strains and multiple methods for cDNA library preparations. We identified alternatively spliced mRNA isoforms in over a half of the multi-exonic fungal genes...
February 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28062664/mapping-eqtls-with-rna-seq-reveals-novel-susceptibility-genes-non-coding-rnas-and-alternative-splicing-events-in-systemic-lupus-erythematosus
#15
Christopher A Odhams, Andrea Cortini, Lingyan Chen, Amy L Roberts, Ana Viñuela, Alfonso Buil, Kerrin S Small, Emmanouil T Dermitzakis, David L Morris, Timothy J Vyse, Deborah S Cunninghame Graham
Studies attempting to functionally interpret complex-disease susceptibility loci by GWAS and eQTL integration have predominantly employed microarrays to quantify gene-expression. RNA-Seq has the potential to discover a more comprehensive set of eQTLs and illuminate the underlying molecular consequence. We examine the functional outcome of 39 variants associated with Systemic Lupus Erythematosus (SLE) through the integration of GWAS and eQTL data from the TwinsUK microarray and RNA-Seq cohort in lymphoblastoid cell lines...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28008720/the-exon-junction-complex-a-lifelong-guardian-of-mrna-fate
#16
REVIEW
Lauren A Woodward, Justin W Mabin, Pooja Gangras, Guramrit Singh
During messenger RNA (mRNA) biogenesis and processing in the nucleus, many proteins are imprinted on mRNAs assembling them into messenger ribonucleoproteins (mRNPs). Some of these proteins remain stably bound within mRNPs and have a long-lasting impact on their fate. One of the best-studied examples is the exon junction complex (EJC), a multiprotein complex deposited primarily 24 nucleotides upstream of exon-exon junctions as a consequence of pre-mRNA splicing. The EJC maintains a stable, sequence-independent, hold on the mRNA until its removal during translation in the cytoplasm...
December 23, 2016: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/27994090/a-common-class-of-transcripts-with-5-intron-depletion-distinct-early-coding-sequence-features-and-n-1-methyladenosine-modification
#17
Can Cenik, Hon Nian Chua, Guramrit Singh, Abdalla Akef, Michael P Snyder, Alexander F Palazzo, Melissa J Moore, Frederick P Roth
Introns are found in 5' untranslated regions (5'UTRs) for 35% of all human transcripts. These 5'UTR introns are not randomly distributed: Genes that encode secreted, membrane-bound and mitochondrial proteins are less likely to have them. Curiously, transcripts lacking 5'UTR introns tend to harbor specific RNA sequence elements in their early coding regions. To model and understand the connection between coding-region sequence and 5'UTR intron status, we developed a classifier that can predict 5'UTR intron status with >80% accuracy using only sequence features in the early coding region...
March 2017: RNA
https://www.readbyqxmd.com/read/27980089/structure-of-a-yeast-step-ii-catalytically-activated-spliceosome
#18
Chuangye Yan, Ruixue Wan, Rui Bai, Gaoxingyu Huang, Yigong Shi
Each cycle of precursor messenger RNA (pre-mRNA) splicing comprises two sequential reactions, first freeing the 5' exon and generating an intron lariat-3' exon and then ligating the two exons and releasing the intron lariat. The second reaction is executed by the step II catalytically activated spliceosome (known as the C* complex). Here, we present the cryo-electron microscopy structure of a C* complex from Saccharomyces cerevisiae at an average resolution of 4.0 angstroms. Compared with the preceding spliceosomal complex (C complex), the lariat junction has been translocated by 15 to 20 angstroms to vacate space for the incoming 3'-exon sequences...
January 13, 2017: Science
https://www.readbyqxmd.com/read/27941783/simulation-based-comprehensive-benchmarking-of-rna-seq-aligners
#19
Giacomo Baruzzo, Katharina E Hayer, Eun Ji Kim, Barbara Di Camillo, Garret A FitzGerald, Gregory R Grant
Alignment is the first step in most RNA-seq analysis pipelines, and the accuracy of downstream analyses depends heavily on it. Unlike most steps in the pipeline, alignment is particularly amenable to benchmarking with simulated data. We performed a comprehensive benchmarking of 14 common splice-aware aligners for base, read, and exon junction-level accuracy and compared default with optimized parameters. We found that performance varied by genome complexity, and accuracy and popularity were poorly correlated...
December 12, 2016: Nature Methods
https://www.readbyqxmd.com/read/27929060/export-of-pirna-precursors-by-ejc-triggers-assembly-of-cytoplasmic-yb-body-in-drosophila
#20
Cynthia Dennis, Emilie Brasset, Arpita Sarkar, Chantal Vaury
PIWI-interacting RNAs (piRNAs) are effectors of transposable element (TE) silencing in the reproductive apparatus. In Drosophila ovarian somatic cells, piRNAs arise from longer single-stranded RNA precursors that are processed in the cytoplasm presumably within the Yb-bodies. piRNA precursors encoded by the flamenco (flam) piRNA cluster accumulate in a single focus away from their sites of transcription. In this study, we identify the exportin complex containing Nxf1 and Nxt1 as required for flam precursor nuclear export...
December 8, 2016: Nature Communications
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