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Rna decay

Yonatan Perez, Shay Menascu, Idan Cohen, Rotem Kadir, Omer Basha, Zamir Shorer, Hila Romi, Gal Meiri, Tatiana Rabinski, Rivka Ofir, Esti Yeger-Lotem, Ohad S Birk
RSRC1, whose polymorphism is associated with altered brain function in schizophrenia, is a member of the serine and arginine rich-related protein family. Through homozygosity mapping and whole exome sequencing we show that RSRC1 mutation causes an autosomal recessive syndrome of intellectual disability, aberrant behaviour, hypotonia and mild facial dysmorphism with normal brain MRI. Further, we show that RSRC1 is ubiquitously expressed, and that the RSRC1 mutation triggers nonsense-mediated mRNA decay of the RSRC1 transcript in patients' fibroblasts...
March 7, 2018: Brain: a Journal of Neurology
Anita H Corbett
A large number of mutations in genes that encode RNA binding proteins cause human disease. Many of these RNA binding proteins mediate key steps in post-transcriptional regulation of gene expression from mRNA processing to eventual decay in the cytoplasm. Surprisingly, these RNA binding proteins, which are ubiquitously expressed and play fundamental roles in gene expression, are often altered in tissue-specific disease. Mutations linked to disease impact nearly every post-transcriptional processing step and cause diverse disease phenotypes in a variety of specific tissues...
March 5, 2018: Current Opinion in Cell Biology
Juan Liu, Kun-Shan Zhang, Bin Hu, Si-Guang Li, Qing Li, Yu-Ping Luo, Yang Wang, Zhi-Feng Deng
Although extensive studies have identified large number of microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) in ischemic stroke, the RNA regulation network response to focal ischemia remains poorly understood. In this study, we simultaneously interrogate the expression profiles of lncRNAs, miRNAs, and mRNAs changes during focal ischemia induced by transient middle cerebral artery occlusion. A set of 1924 novel lncRNAs were identified and may involve brain injury and DNA repair as revealed by coexpression network analysis...
2018: BioMed Research International
Huawen Lin, Zhengyan Zhang, Carlo Iomini, Susan K Dutcher
Intraflagellar transport moves proteins in and out of flagella/cilia and it is essential for the assembly of these organelles. Using whole-genome sequencing, we identified splice site mutations in two IFT genes, IFT81 ( fla9 ) and IFT121 ( ift121-2 ), which lead to flagellar assembly defects in the unicellular green alga Chlamydomonas reinhardtii The splicing defects in these ift mutants are partially corrected by mutations in two conserved spliceosome proteins, DGR14 and FRA10. We identified a dgr14 deletion mutant, which suppresses the 3' splice site mutation in IFT81 , and a frameshift mutant of FRA10 , which suppresses the 5' splice site mutation in IFT121 Surprisingly, we found dgr14-1 and fra10 mutations suppress both splice site mutations...
March 2018: Open Biology
Ruben D Arroyo-Olarte, Ignacio Martínez, Mayra Cruz-Rivera, Fela Mendlovic, Bertha Espinoza
BACKGROUND: Trypanosoma cruzi is a protozoan parasite and an etiological agent of Chagas disease. There is a wide variability in the clinical outcome of its infection, ranging from asymptomatic individuals to those with chronic fatal mega syndromes. Both parasite and host factors, as well as their interplay, are thought to be involved in the process. OBJECTIVES: To evaluate the resistance to complement-mediated killing in two T. cruzi TcI strains with differential virulence and the subsequent effect on their infectivity in mammalian cells...
February 19, 2018: Memórias do Instituto Oswaldo Cruz
Chih-Hang Anthony Tang, Shiun Chang, Adrienne W Paton, James C Paton, Dmitry I Gabrilovich, Hidde L Ploegh, Juan R Del Valle, Chih-Chi Andrew Hu
To relieve endoplasmic reticulum (ER) stress, IRE1 splices XBP1 messenger RNA (mRNA) or engages regulated IRE1-dependent decay (RIDD) of other mRNAs. Upon XBP1 deficiency, IRE1 switches to perform RIDD. We examined IRE1 in XBP1-deficient B cells and discovered that IRE1 undergoes phosphorylation at S729. We generated an anti-phospho-S729 antibody to investigate such phosphorylation. Compared with pharmacological ER stress inducers or Toll-like receptor ligands, the bacterial subtilase cytotoxin has an unusual capability in causing rapid and strong phosphorylation at S729 and triggering B cells to express spliced XBP1...
March 6, 2018: Journal of Cell Biology
Fadia Ibrahim, Manolis Maragkakis, Panagiotis Alexiou, Zissimos Mourelatos
mRNAs transmit the genetic information that dictates protein production and are a nexus for numerous pathways that regulate gene expression. The prevailing view of canonical mRNA decay is that it is mediated by deadenylation and decapping followed by exonucleolysis from the 3' and 5' ends. By developing Akron-seq, a novel approach that captures the native 3' and 5' ends of capped and polyadenylated RNAs, respectively, we show that canonical human mRNAs are subject to repeated cotranslational and ribosome-phased endonucleolytic cuts at the exit site of the mRNA ribosome channel, in a process that we term ribothrypsis...
March 5, 2018: Nature Structural & Molecular Biology
Lisa Hartmann, Theresa Wießner, Andreas Wachter
Alternative splicing (AS) is prevalent in higher eukaryotes, and generation of different AS variants is tightly regulated. Widespread AS occurs in response to altered light conditions and plays a critical role in seedling photomorphogenesis, but despite its frequency and effect on plant development, the functional role of AS remains unknown for most splicing variants. Here, we characterized the light-dependent AS variants of the gene encoding the splicing regulator Serine/Arginine-rich protein SR30 in Arabidopsis (Arabidopsis thaliana)...
March 1, 2018: Plant Physiology
Esteban D Erben
From synthesis to decay, mRNA associates with RNA-binding proteins (RBPs) establishing dynamic ribonucleoprotein particles (RNPs). Understanding the composition and function of RNPs is fundamental to understanding how eukaryotic mRNAs are controlled. This is especially relevant for trypanosomes and related kinetoplastid parasites, which mostly rely on post-transcriptional mechanisms to control gene expression. Crucial for trypanosome differentiation, development, or even response to heat shock, RBPs are known to be essential modulators of diverse molecular processes...
February 2018: Current Genomics
Timo Weinrich, Eva A Jaumann, Ute Scheffer, Thomas F Prisner, Michael W Göbel
EPR studies on RNA are complicated by three major obstacles related to the chemical nature of nitroxide spin labels: Decomposition while oligonucleotides are chemically synthesized, further decay during enzymatic strand ligation and undetected changes in conformational equilibria by the steric demand of the label. Here we present possible solutions for all three problems: A 2-nitrobenzyloxymethyl protective group for nitroxides, stable under all conditions of chemical RNA synthesis that can be removed photochemically...
February 27, 2018: Chemistry: a European Journal
Florent Busi, Véronique Arluison, Philippe Régnier
Regulation of RNA turnover is of utmost importance for controlling the concentration of transcripts and consequently cellular protein levels. Among the processes controlling RNA decay, small noncoding regulatory RNAs (sRNAs) have recently emerged as major new players. In this chapter, we describe and discuss protocols that can be used to measure sRNA concentration in vivo and to assess sRNA decay rates in Gram-negative bacteria. Precisely, we focus our analyses on the Escherichia coli Gram-negative bacterium as a model...
2018: Methods in Molecular Biology
Cédric Nadiras, Annie Schwartz, Mildred Delaleau, Marc Boudvillain
Besides their well-known posttranscriptional effects on mRNA translation and decay, sRNAs and associated RNA chaperones (e.g., Hfq, CsrA) sometimes regulate gene expression at the transcriptional level. In this case, the sRNA-dependent machinery modulates the activity of the transcription termination factor Rho, a ring-shaped RNA translocase/helicase that dissociates transcription elongation complexes at specific loci of the bacterial genome. Here, we describe biochemical assays to detect Rho-dependent termination signals in genomic regions of interest and to assess the effects of sRNAs and/or associated RNA chaperones on such signals...
2018: Methods in Molecular Biology
Elodie Choque, Claudia Schneider, Olivier Gadal, Christophe Dez
Ribosome biogenesis requires more than 200 trans-acting factors to achieve the correct production of the two mature ribosomal subunits. Here, we have identified Efg1 as a novel, nucleolar ribosome biogenesis factor in Saccharomyces cerevisiae that is directly linked to the surveillance of pre-40S particles. Depletion of Efg1 impairs early pre-rRNA processing, leading to a strong decrease in 18S rRNA and 40S subunit levels and an accumulation of the aberrant 23S rRNA. Using Efg1 as bait, we revealed a novel degradation pathway of the 23S rRNA...
February 22, 2018: Nucleic Acids Research
Natalia O Kalinina, Svetlana Makarova, Antonida Makhotenko, Andrew J Love, Michael Taliansky
The nucleolus is the most conspicuous domain in the eukaryotic cell nucleus, whose main function is ribosomal RNA (rRNA) synthesis and ribosome biogenesis. However, there is growing evidence that the nucleolus is also implicated in many other aspects of cell biology, such as regulation of cell cycle, growth and development, senescence, telomerase activity, gene silencing, responses to biotic and abiotic stresses. In the first part of the review, we briefly assess the traditional roles of the plant nucleolus in rRNA synthesis and ribosome biogenesis as well as possible functions in other RNA regulatory pathways such as splicing, nonsense-mediated mRNA decay and RNA silencing...
2018: Frontiers in Plant Science
Anas M Alazami, Maryam Al-Helale, Safa Alhissi, Bandar Al-Saud, Huda Alajlan, Dorota Monies, Zeeshan Shah, Mohamed Abouelhoda, Rand Arnaout, Hasan Al-Dhekri, Nouf S Al-Numair, Hazem Ghebeh, Farrukh Sheikh, Hamoud Al-Mousa
Combined immunodeficiencies are a heterogeneous collection of primary immune disorders that exhibit defects in T cell development or function, along with impaired B cell activity even in light of normal B cell maturation. CARMIL2 (RLTPR) is a protein involved in cytoskeletal organization and cell migration, which also plays a role in CD28 co-signaling of T cells. Mutations in this protein have recently been reported to cause a novel primary immunodeficiency disorder with variable phenotypic presentations. Here, we describe seven patients from three unrelated, consanguineous multiplex families that presented with dermatitis, esophagitis, and recurrent skin and chest infections with evidence of combined immunodeficiency...
2018: Frontiers in Immunology
Jianjian Wei, Jie Zhou, Kitling Cheng, Jie Wu, Zhifeng Zhong, Yingchao Song, Changwen Ke, Hui-Ling Yen, Yuguo Li
Interspecies transmissions of avian influenza viruses (AIV) occur at the human-poultry interface, among which the live poultry markets (LPMs) are easily assessed by urban residents. Thousands of live poultry from different farms arrive daily at wholesale markets before being sold to retail markets. We assessed the risk of AIV downwind spread via airborne particles from a representative wholesale market in Guangzhou. Air samples were collected using the cyclone-based NIOSH bioaerosol samplers at different locations inside a wholesale market, and viral RNA and avian 18S RNA were quantified using quantitative real-time RT-PCR...
January 2018: Building and Environment
Huilin Huang, Hengyou Weng, Wenju Sun, Xi Qin, Hailing Shi, Huizhe Wu, Boxuan Simen Zhao, Ana Mesquita, Chang Liu, Celvie L Yuan, Yueh-Chiang Hu, Stefan Hüttelmaier, Jennifer R Skibbe, Rui Su, Xiaolan Deng, Lei Dong, Miao Sun, Chenying Li, Sigrid Nachtergaele, Yungui Wang, Chao Hu, Kyle Ferchen, Kenneth D Greis, Xi Jiang, Minjie Wei, Lianghu Qu, Jun-Lin Guan, Chuan He, Jianhua Yang, Jianjun Chen
N6 -methyladenosine (m6 A) is the most prevalent modification in eukaryotic messenger RNAs (mRNAs) and is interpreted by its readers, such as YTH domain-containing proteins, to regulate mRNA fate. Here, we report the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; including IGF2BP1/2/3) as a distinct family of m6 A readers that target thousands of mRNA transcripts through recognizing the consensus GG(m6 A)C sequence. In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6 A-dependent manner under normal and stress conditions and therefore affect gene expression output...
March 2018: Nature Cell Biology
Jung-Chun Lin
Alternative splicing has been widely demonstrated to function as pivotal regulation in specifying cellular fates and biological functions. The relative expression or cellular localization of a splicing factor constitutes an important mechanism in spatiotemporal programming of cell- and stage-specific splicing profiles. In this study, results of deep RNA-sequencing (RNA-Seq) analyses first revealed the reprogrammed splicing profile and reduced expression of serine/arginine-rich splicing factor protein kinase 1 (SRPK1) throughout the development of brown adipose tissue (BAT)...
February 20, 2018: Biochimica et Biophysica Acta
Kamaludin Dingle, Chico Q Camargo, Ard A Louis
Many systems in nature can be described using discrete input-output maps. Without knowing details about a map, there may seem to be no a priori reason to expect that a randomly chosen input would be more likely to generate one output over another. Here, by extending fundamental results from algorithmic information theory, we show instead that for many real-world maps, the a priori probability P(x) that randomly sampled inputs generate a particular output x decays exponentially with the approximate Kolmogorov complexity [Formula: see text] of that output...
February 22, 2018: Nature Communications
Vladimir Despic, Karla M Neugebauer
Following fertilization, embryos develop for a substantial amount of time with a transcriptionally silent genome. Thus, early development is maternally programmed, as it solely relies on RNAs and proteins that are provided by the female gamete. However, these maternal instructions are not sufficient to support later steps of embryogenesis and are therefore gradually replaced by novel products synthesized from the zygotic genome. This switch in the origin of molecular players that drive early development is known as the maternal-to-zygotic transition (MZT)...
February 21, 2018: Journal of Cell Science
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