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https://www.readbyqxmd.com/read/28328949/mcpip1-alias-regnase-1-binds-and-cleaves-mrna-of-c-ebp%C3%AE
#1
Barbara Lipert, Mateusz Wilamowski, Andrzej Gorecki, Jolanta Jura
CCAAT/enhancer-binding protein beta (C/EBPβ) is a transcription factor controlling a broad range of genes essential for homeostasis, including genes related to immune functions, inflammation, metabolism and growth. Monocyte chemoattractant protein-1-induced protein 1 (MCPIP1) also called as Regnase-1 is an RNase and has been shown to decrease the stability of short-lived transcripts coding for inflammation-related proteins, including IL-1β, IL-6, IL-2, IL-8, IL-12b, IER-3, c-Rel. We found previously that the half-life of the C/EBPβ transcript is regulated by MCPIP...
2017: PloS One
https://www.readbyqxmd.com/read/28323884/a-system-for-coordinated-analysis-of-translational-readthrough-and-nonsense-mediated-mrna-decay
#2
Stacey L Baker, J Robert Hogg
The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs containing premature termination codons, limiting the expression of potentially deleterious truncated proteins. This activity positions the pathway as a regulator of the severity of genetic diseases caused by nonsense mutations. Because many genetic diseases result from nonsense alleles, therapeutics inducing readthrough of premature termination codons and/or inhibition of NMD have been of great interest. Several means of enhancing translational readthrough have been reported to concomitantly inhibit NMD efficiency, but tools for systematic analysis of mammalian NMD inhibition by translational readthrough are lacking...
2017: PloS One
https://www.readbyqxmd.com/read/28318367/combinatorial-control-of-messenger-rnas-by-pumilio-nanos-and-brain-tumor-proteins
#3
René M Arvola, Chase A Weidmann, Traci M Tanaka Hall, Aaron C Goldstrohm
Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of three Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurological processes. Here we synthesize thirty years of research with new insights into their molecular functions and mechanisms of action...
March 20, 2017: RNA Biology
https://www.readbyqxmd.com/read/28298237/irfinder-assessing-the-impact-of-intron-retention-on-mammalian-gene-expression
#4
Robert Middleton, Dadi Gao, Aubin Thomas, Babita Singh, Amy Au, Justin J-L Wong, Alexandra Bomane, Bertrand Cosson, Eduardo Eyras, John E J Rasko, William Ritchie
Intron retention (IR) occurs when an intron is transcribed into pre-mRNA and remains in the final mRNA. We have developed a program and database called IRFinder to accurately detect IR from mRNA sequencing data. Analysis of 2573 samples showed that IR occurs in all tissues analyzed, affects over 80% of all coding genes and is associated with cell differentiation and the cell cycle. Frequently retained introns are enriched for specific RNA binding protein sites and are often retained in clusters in the same gene...
March 15, 2017: Genome Biology
https://www.readbyqxmd.com/read/28292421/rna-methylation-clears-the-way
#5
Cassandra Kontur, Antonio Giraldez
During the maternal-to-zygotic transition, maternal mRNAs are cleared by multiple distinct but interrelated pathways. A recent study in Nature by Zhao et al. (2017) finds that YTHDF2, a reader of N(6)- methylation, facilitates maternal mRNA decay, introducing an additional facet of control over transcript fate and developmental reprogramming.
March 13, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28288699/longevity-regulation-by-nmd-mediated-mrna-quality-control
#6
Heehwa G Son, Seung-Jae V Lee
Proper maintenance of biological components is crucial for longevity and healthy aging. Although the role of homeostatic maintenance systems for DNA and protein in longevity is established, it remained largely unknown for RNA. In our recent work, we show that nonsense-mediated mRNA decay (NMD) promotes longevity in the roundworm C. elegans by enhancing RNA quality control. We find that the activity of NMD decreases during aging, raising the possibility that RNA quality declines in old animals. We then show that key components of NMD complex are required for long lifespan in C...
March 14, 2017: BMB Reports
https://www.readbyqxmd.com/read/28287719/polyatomic-ab-initio-complex-potential-energy-surfaces-illustration-of-ultracold-collisions
#7
Debarati Bhattacharya, Anael Ben-Asher, Idan Haritan, Mariusz Pawlak, Arie Landau, Nimrod Moiseyev
Resonances are metastable states that decay after a finite period of time. These states play a role in many physical processes. For example, in recent cold collision experiments, autoionization from a resonance state was observed. Complementing such observations with theory provide insight into the reaction dynamics under study. Theoretical investigation of autoionization processes is enabled via complex potential energy surfaces (CPESs), where the real and imaginary parts, respectively, provide the energy and decay rate of the system...
March 13, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28287067/translational-control-of-mrnas-by-3-untranslated-region-binding-proteins
#8
Akio Yamashita, Osamu Takeuchi
Eukaryotic gene expression is precisely regulated at all points between transcription and translation. In this review, we focus on translational control mediated by the 3'-untranslated regions (UTRs) of mRNAs. mRNA 3'-UTRs contain cis-acting elements that function in the regulation of protein translation or mRNA decay. RNA binding proteins that bind to these cis-acting elements regulate mRNA translation via various mechanisms targeting the mRNA cap structure, the eukaryotic initiation factor 4E (eIF4E)-eIF4G complex, ribosomes, and the poly (A) tail...
March 13, 2017: BMB Reports
https://www.readbyqxmd.com/read/28286508/global-transcriptome-analysis-and-identification-of-differentially-expressed-genes-in-strawberry-after-preharvest-application-of-benzothiadiazole-and-chitosan
#9
Lucia Landi, Rita M De Miccolis Angelini, Stefania Pollastro, Erica Feliziani, Franco Faretra, Gianfranco Romanazzi
The use of resistance inducers is a novel strategy to elicit defense responses in strawberry fruit to protect against preharvest and postharvest decay. However, the mechanisms behind the specific resistance inducers are not completely understood. Here, global transcriptional changes in strawberry fruit were investigated using RNA-Seq technology. Preharvest, benzothiadiazole (BTH) and chitosan were applied to the plant canopy, and the fruit were harvested at 6, 12, and 24 h post-treatment. Overall, 5,062 and 5,210 differentially expressed genes (fold change ≥ 2) were identified in these fruits under the BTH and chitosan treatments, respectively, as compared to the control expression...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28283058/5-end-nicotinamide-adenine-dinucleotide-cap-in-human-cells-promotes-rna-decay-through-dxo-mediated-denadding
#10
Xinfu Jiao, Selom K Doamekpor, Jeremy G Bird, Bryce E Nickels, Liang Tong, Ronald P Hart, Megerditch Kiledjian
Eukaryotic mRNAs generally possess a 5' end N7 methyl guanosine (m(7)G) cap that promotes their translation and stability. However, mammalian mRNAs can also carry a 5' end nicotinamide adenine dinucleotide (NAD(+)) cap that, in contrast to the m(7)G cap, does not support translation but instead promotes mRNA decay. The mammalian and fungal noncanonical DXO/Rai1 decapping enzymes efficiently remove NAD(+) caps, and cocrystal structures of DXO/Rai1 with 3'-NADP(+) illuminate the molecular mechanism for how the "deNADding" reaction produces NAD(+) and 5' phosphate RNA...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28277935/the-pre-mrna-retention-and-splicing-complex-controls-expression-of-the-mediator-subunit-med20
#11
Yang Zhou, Marcus J O Johansson
The heterotrimeric pre-mRNA retention and splicing (RES) complex, consisting of Bud13p, Snu17p and Pml1p, promotes splicing and nuclear retention of a subset of intron-containing pre-mRNAs. Yeast cells deleted for individual RES genes show growth defects that are exacerbated at elevated temperatures. Although the growth phenotypes correlate to the splicing defects in the individual mutants, the underlying mechanism is unknown. Here, we show that the temperature sensitive (Ts) growth phenotype of bud13Δ and snu17Δ cells is a consequence of inefficient splicing of MED20 pre-mRNA, which codes for a subunit of the Mediator complex; a co-regulator of RNA polymerase II transcription...
February 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28277929/both-exo-and-endo-nucleolytic-activities-of-rnase-j1-from-staphylococcus-aureus-are-manganese-dependent-and-active-on-triphosphorylated-5-ends
#12
Stéphane Hausmann, Vanessa Andrade Guimarães, Dominique Garcin, Natalia Baumann, Patrick Linder, Peter Redder
RNA decay and RNA maturation are important steps in the regulation of bacterial gene expression. RNase J, which is present in about half of bacterial species, has been shown to possess both endo- and 5' to 3' exo-ribonuclease activities. The exonucleolytic activity is clearly involved in the degradation of mRNA and in the maturation of at least the 5'end of 16S rRNA in the two Firmicutes Staphylococcus aureus and Bacillus subtilis. The endoribonuclease activity of RNase J from a number of species has been shown to be weak in vitro and 3-D structural data of different RNase J orthologs has not provided a clear explanation for the molecular basis of this activity...
March 1, 2017: RNA Biology
https://www.readbyqxmd.com/read/28276498/the-impact-of-the-rbm4-initiated-splicing-cascade-on-modulating-the-carcinogenic-signature-of-colorectal-cancer-cells
#13
Jung-Chun Lin, Yuan-Chii Lee, Yu-Chih Liang, Yang C Fann, Kory R Johnson, Ying-Ju Lin
A growing body of studies has demonstrated that dysregulated splicing profiles constitute pivotal mechanisms for carcinogenesis. In this study, we identified discriminative splicing profiles of colorectal cancer (CRC) cells compared to adjacent normal tissues using deep RNA-sequencing (RNA-seq). The RNA-seq results and cohort studies indicated a relatively high ratio of exon 4-excluded neuro-oncological ventral antigen 1 (Nova1(-4)) and intron 2-retained SRSF6 (SRSF6(+intron 2)) transcripts in CRC tissues and cell lines...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28276441/rna-surveillance-via-nonsense-mediated-mrna-decay-is-crucial-for-longevity-in-daf-2-insulin-igf-1-mutant-c-elegans
#14
Heehwa G Son, Mihwa Seo, Seokjin Ham, Wooseon Hwang, Dongyeop Lee, Seon Woo A An, Murat Artan, Keunhee Seo, Rachel Kaletsky, Rachel N Arey, Youngjae Ryu, Chang Man Ha, Yoon Ki Kim, Coleen T Murphy, Tae-Young Roh, Hong Gil Nam, Seung-Jae V Lee
Long-lived organisms often feature more stringent protein and DNA quality control. However, whether RNA quality control mechanisms, such as nonsense-mediated mRNA decay (NMD), which degrades both abnormal as well as some normal transcripts, have a role in organismal aging remains unexplored. Here we show that NMD mediates longevity in C. elegans strains with mutations in daf-2/insulin/insulin-like growth factor 1 receptor. We find that daf-2 mutants display enhanced NMD activity and reduced levels of potentially aberrant transcripts...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28275056/ksrp-promotes-post-transcriptional-destabilization-of-spry4-transcripts-in-non-small-cell-lung-cancer
#15
Rama Kamesh Bikkavilli, Sereke Adam Zerayesus, Michelle Van Scoyk, Lora Wilson, Pei-Ying Wu, Abhinaya Baskaran, Ke Tang, Syed Raheem, Blain A Samuelson, Narsa M Reddy, Sekhar P Reddy, Carlyne D Cool, Beata Kosmider, Sreedevi Avasarala, Robert A Winn
AU-rich element binding proteins (ARE-BPs) offer post-transcriptional regulation of gene expression via physical interaction and recruitment of RNA decay machinery to the AU-rich elements within the 3'UTR of the target transcripts. However, the role of ARE-BPs in lung cancer remains poorly understood. In this study, we have identified that K-homology splicing regulatory protein (KSRP), an ARE-BP, is robustly up-regulated in human lung cancer. Importantly, Kaplan-Meier survival analysis indicated that elevated KSRP expression was correlated with poor overall survival of lung cancer patients...
March 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28272342/the-characterization-of-gsdmb-splicing-and-backsplicing-profiles-identifies-novel-isoforms-and-a-circular-rna-that-are-dysregulated-in-multiple-sclerosis
#16
Giulia Cardamone, Elvezia Maria Paraboschi, Valeria Rimoldi, Stefano Duga, Giulia Soldà, Rosanna Asselta
Abnormalities in alternative splicing (AS) are emerging as recurrent features in autoimmune diseases (AIDs). In particular, a growing body of evidence suggests the existence of a pathogenic association between a generalized defect in splicing regulatory genes and multiple sclerosis (MS). Moreover, several studies have documented an unbalance in alternatively-spliced isoforms in MS patients possibly contributing to the disease etiology. In this work, using a combination of PCR-based techniques (reverse-transcription (RT)-PCR, fluorescent-competitive, real-time, and digital RT-PCR assays), we investigated the alternatively-spliced gene encoding Gasdermin B, GSDMB, which was repeatedly associated with susceptibility to asthma and AIDs...
March 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28261246/possible-role-of-mads-affecting-flowering-3-and-b-box-domain-protein-19-in-flowering-time-regulation-of-arabidopsis-mutants-with-defects-in-nonsense-mediated-mrna-decay
#17
Zeeshan Nasim, Muhammad Fahim, Ji Hoon Ahn
Eukaryotic cells use nonsense-mediated mRNA decay (NMD) to clear aberrant mRNAs from the cell, thus preventing the accumulation of truncated proteins. In Arabidopsis, two UP-Frameshift (UPF) proteins, UPF1 and UPF3, play a critical role in NMD. Although deficiency of UPF1 and UPF3 leads to various developmental defects, little is known about the mechanism underlying the regulation of flowering time by NMD. Here, we showed that the upf1-5 and upf3-1 mutants had a late-flowering phenotype under long-day conditions and the upf1-5 upf3-1 double mutants had an additive effect in delaying flowering time...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28257696/nuclear-decay-factors-crack-up-mrna
#18
Agnieszka Tudek, Manfred Schmid, Torben Heick Jensen
In this issue of Molecular Cell, Bresson et al. (2017) show that the nuclear RNA decay factors Nab3 and Mtr4 reshape the coding transcriptome during glucose starvation in budding yeast, placing nuclear mRNA metabolism as an important contributor of gene expression regulation.
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28240253/proteomic-analysis-of-the-mediator-complex-interactome-in-saccharomyces-cerevisiae
#19
Henriette Uthe, Jens T Vanselow, Andreas Schlosser
Here we present the most comprehensive analysis of the yeast Mediator complex interactome to date. Particularly gentle cell lysis and co-immunopurification conditions allowed us to preserve even transient protein-protein interactions and to comprehensively probe the molecular environment of the Mediator complex in the cell. Metabolic (15)N-labeling thereby enabled stringent discrimination between bona fide interaction partners and nonspecifically captured proteins. Our data indicates a functional role for Mediator beyond transcription initiation...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28238534/structural-insights-into-a-unique-dimeric-dead-box-helicase-csha-that-promotes-rna-decay
#20
Jennifer Huen, Chia-Liang Lin, Bagher Golzarroshan, Wan-Li Yi, Wei-Zen Yang, Hanna S Yuan
CshA is a dimeric DEAD-box helicase that cooperates with ribonucleases for mRNA turnover. The molecular mechanism for how a dimeric DEAD-box helicase aids in RNA decay remains unknown. Here, we report the crystal structure and small-angle X-ray scattering solution structure of the CshA from Geobacillus stearothermophilus. In contrast to typical monomeric DEAD-box helicases, CshA is exclusively a dimeric protein with the RecA-like domains of each protomer forming a V-shaped structure. We show that the C-terminal domains protruding outward from the tip of the V-shaped structure is critical for mediating strong RNA binding and is crucial for efficient RNA-dependent ATP hydrolysis...
March 7, 2017: Structure
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