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  • An open interface in the pre-80S ribosome coordinated by ribosome assembly factors Tsr1 and Dim1 enables temporal regulation of Fap7.
    RNA (IF 4.32) Pub Date : 2020-11-20
    Jay Rai; Melissa D. Parker; Haina Huang; Stefan Choy; Homa Ghalei; Matthew C. Johnson; Katrin Karbstein; M. Elizabeth Stroupe

    During their maturation, nascent 40S subunits enter a translation-like quality control cycle, where they are joined by mature 60S subunits to form 80S-like ribosomes. While these assembly intermediates are essential for maturation and quality control, how they form, and how their structure promotes quality control remains unknown. To address these questions, we determined the structure of an 80S-like

    更新日期:2020-11-21
  • Post-transcriptional modifications at the 37th position in the anticodon stem loop of tRNA: Structural insights from MD simulations
    RNA (IF 4.32) Pub Date : 2020-11-19
    Preethi Seelam Prabhakar; Nathania Takyi; Stacey Wetmore

    Transfer RNA (tRNA) is the most diversely modified RNA. Although the strictly conserved purine position 37 in the anticodon stem loop (ASL) undergoes a wide assortment of modifications that are phylogenetically distributed, we do not yet fully understand the roles of these modifications. To provide molecular-level details for how such modifications impact the structure and function of tRNA, molecular

    更新日期:2020-11-19
  • RNA partitioning into stress granules is based on the summation of multiple interactions
    RNA (IF 4.32) Pub Date : 2020-11-16
    Tyler Matheny; Briana Van Treeck; Thao Ngoc Huynh; Roy Parker

    Stress granules (SGs) are stress-induced RNA-protein assemblies formed from a complex transcriptome of untranslating ribonucleoproteins (RNPs). Although RNAs can be either enriched or depleted from SGs, the rules that dictate RNA partitioning into SGs are unknown. We demonstrate that the SG-enriched NORAD RNA is sufficient to enrich a reporter RNA within SGs through the combined effects of multiple

    更新日期:2020-11-17
  • RNA: Author Index for Volume 26, 2020
    RNA (IF 4.32) Pub Date : 2020-12-01

    Abdullahu, L., 373

    更新日期:2020-11-16
  • RNA: Reviewers for Volume 26, 2020
    RNA (IF 4.32) Pub Date : 2020-12-01

    The editors wish to thank the following individuals whose efforts in reviewing papers for RNA in the past year are greatly appreciated.

    更新日期:2020-11-16
  • Single-pass transcription by T7 RNA polymerase.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Luiz F M Passalacqua,Armine I Dingilian,Andrej Luptak

    RNA molecules can be conveniently synthesized in vitro by the T7 RNA polymerase (T7 RNAP). In some experiments, such as cotranscriptional biochemical analyses, continuous synthesis of RNA is not desired. Here, we propose a method for a single-pass transcription that yields a single transcript per template DNA molecule using the T7 RNAP system. We hypothesized that stalling the polymerase downstream

    更新日期:2020-11-16
  • Chemical shifts-based similarity restraints improve accuracy of RNA structures determined via NMR.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Chad Lawrence,Alexander V Grishaev

    Determination of structure of RNA via NMR is complicated in large part by the lack of a precise parameterization linking the observed chemical shifts to the underlying geometric parameters. In contrast to proteins, where numerous high-resolution crystal structures serve as coordinate templates for this mapping, such models are rarely available for smaller oligonucleotides accessible via NMR, or they

    更新日期:2020-11-16
  • Solution structure and RNA-binding of a minimal ProQ-homolog from Legionella pneumophila (Lpp1663)
    RNA (IF 4.32) Pub Date : 2020-12-01
    Carina Immer; Carolin Hacker; Jens Wöhnert

    Small regulatory RNAs (sRNAs) play an important role for posttranscriptional gene regulation in bacteria. sRNAs recognize their target messenger RNAs (mRNAs) by base-pairing, which is often facilitated by interactions with the bacterial RNA-binding proteins Hfq or ProQ. The FinO/ProQ RNA-binding protein domain was first discovered in the bacterial repressor of conjugation, FinO. Since then, the functional

    更新日期:2020-11-16
  • Termi-Luc: a versatile assay to monitor full-protein release from ribosomes.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Denis Susorov,Shawn Egri,Andrei A Korostelev

    Termination of protein biosynthesis is an essential step of gene expression, during which a complete functional protein is released from the ribosome. Premature or inefficient termination results in truncated, nonfunctional, or toxic proteins that may cause disease. Indeed, more than 10% of human genetic diseases are caused by nonsense mutations leading to premature termination. Efficient and sensitive

    更新日期:2020-11-16
  • Alternative conformations and motions adopted by 30S ribosomal subunits visualized by cryo-electron microscopy
    RNA (IF 4.32) Pub Date : 2020-12-01
    Dushyant Jahagirdar; Vikash Jha; Kaustuv Basu; Josue Gomez-Blanco; Javier Vargas; Joaquin Ortega

    It is only after recent advances in cryo-electron microscopy that it is now possible to describe at high-resolution structures of large macromolecules that do not crystalize. Purified 30S subunits interconvert between an “active” and “inactive” conformation. The active conformation was described by crystallography in the early 2000s, but the structure of the inactive form at high resolution remains

    更新日期:2020-11-16
  • Physiologic RNA targets and refined sequence specificity of coronavirus EndoU
    RNA (IF 4.32) Pub Date : 2020-12-01
    Rachel Ancar; Yize Li; Eveline Kindler; Daphne A. Cooper; Monica Ransom; Volker Thiel; Susan R. Weiss; Jay R. Hesselberth; David J. Barton

    Coronavirus EndoU inhibits dsRNA-activated antiviral responses; however, the physiologic RNA substrates of EndoU are unknown. In this study, we used mouse hepatitis virus (MHV)-infected bone marrow–derived macrophage (BMM) and cyclic phosphate cDNA sequencing to identify the RNA targets of EndoU. EndoU targeted viral RNA, cleaving the 3′ side of pyrimidines with a strong preference for U↓A and C↓A

    更新日期:2020-11-16
  • The origin of the high stability of 3'-terminal uridine tetrads. The contributions of hydrogen bonding, stacking interactions and steric factors evaluated using modified oligonucleotide analogs.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Witold Andralojc,Karol Pasternak,Joanna Sarzynska,Karolina Zielinska,Ryszard Kierzek,Zofia Gdaniec

    RNA G-quadruplexes fold almost exclusively into parallel-stranded structures and thus display much less structural diversity than their DNA counterparts. However, also among RNA G-quadruplexes peculiar structural elements can be found which are capable of reshaping the physico-chemical properties of the folded structure. A striking example is provided by a uridine tetrad (U-tetrad) placed on the 3′-terminus

    更新日期:2020-11-16
  • Comparative patterns of modified nucleotides in individual tRNA species from a mesophilic and two thermophilic archaea
    RNA (IF 4.32) Pub Date : 2020-12-01
    Philippe Wolff; Claire Villette; Julie Zumsteg; Dimitri Heintz; Laura Antoine; Béatrice Chane-Woon-Ming; Louis Droogmans; Henri Grosjean; Eric Westhof

    To improve and complete our knowledge of archaeal tRNA modification patterns, we have identified and compared the modification pattern (type and location) in tRNAs of three very different archaeal species, Methanococcus maripaludis (a mesophilic methanogen), Pyrococcus furiosus (a hyperthermophile thermococcale), and Sulfolobus acidocaldarius (an acidophilic thermophilic sulfolobale). Most abundant

    更新日期:2020-11-16
  • NineTeen Complex-subunit Salsa is required for efficient splicing of a subset of introns and dorsal-ventral patterning.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Om S Rathore,Rui D Silva,Mariana Ascensao-Ferreira,Ricardo Matos,Celia Carvalho,Bruno Marques,Margarida N Tiago,Pedro Prudencio,Raquel P Andrade,Jean-Yves Roignant,Nuno L Barbosa-Morais,Rui Goncalo Martinho

    The NineTeen Complex (NTC), also known as pre-mRNA-processing factor 19 (Prp19) complex, regulates distinct spliceosome conformational changes necessary for splicing. During Drosophila midblastula transition, splicing is particularly sensitive to mutations in NTC-subunit Fandango, which suggests differential requirements of NTC during development. We show that NTC-subunit Salsa, the Drosophila ortholog

    更新日期:2020-11-16
  • The shift from early to late types of ribosomes in zebrafish development involves changes at a subset of rRNA 2'-O-Me sites.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Sowmya Ramachandran,Nicolai Krogh,Tor Erik Jørgensen,Steinar Daae Johansen,Henrik Nielsen,Igor Babiak

    During zebrafish development, an early type of rRNA is gradually replaced by a late type that is substantially different in sequence. We applied RiboMeth-seq to rRNA from developmental stages for profiling of 2′-O-Me, to learn if changes in methylation pattern were a component of the shift. We compiled a catalog of 2′-O-Me sites and cognate box C/D guide RNAs comprising 98 high-confidence sites, including

    更新日期:2020-11-16
  • RNA-seq accuracy and reproducibility for the mapping and quantification of influenza defective viral genomes.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Jeremy Boussier,Sandie Munier,Emna Achouri,Bernadette Crescenzo-Chaigne,Sylvie Behillil,Vincent Enouf,Sylvie van der Werf,Nadia Naffakh

    Like most RNA viruses, influenza viruses generate defective viral genomes (DVGs) with large internal deletions during replication. There is accumulating evidence supporting a biological relevance of such DVGs. However, further understanding of the molecular mechanisms that underlie the production and biological activity of DVGs is conditioned upon the sensitivity and accuracy of detection methods,

    更新日期:2020-11-16
  • Resolution of polycistronic RNA by SL2 trans-splicing is a widely-conserved nematode trait.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Marius Wenzel,Christopher Johnston,Berndt Müller,Jonathan Pettitt,Bernadette Connolly

    Spliced leader trans-splicing is essential for the processing and translation of polycistronic RNAs generated by eukaryotic operons. In C. elegans, a specialized spliced leader, SL2, provides the 5′ end for uncapped pre-mRNAs derived from polycistronic RNAs. Studies of other nematodes suggested that SL2-type trans-splicing is a relatively recent innovation, confined to Rhabditina, the clade containing

    更新日期:2020-11-16
  • Interrogation of Highly Structured RNA with Multicomponent Deoxyribozyme Probes at Ambient Temperatures.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Adam J Reed,Ryan J Sapia,Charles Dowis,Sheila Solarez,Yulia V Gerasimova

    Molecular analysis of RNA through hybridization with sequence-specific probes is challenging due to the intrinsic ability of RNA molecules to form stable secondary and tertiary structures. To overcome the energy barrier toward the probe–RNA complex formation, the probes are made of artificial nucleotides, which are more expensive than their natural counterparts and may still be inefficient. Here, we

    更新日期:2020-11-16
  • Site-specific and mRNA-specific control of accurate mRNA editing by a helicase complex in trypanosomes.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Vikas Kumar,Alasdair Ivens,Zachary Goodall,Joshua Meehan,Pawan K Doharey,Andrew Hillhouse,Daniel O Hurtado,James J Cai,Xiuren Zhang,Achim Schnaufer,Jorge Cruz-Reyes

    Trypanosome U-insertion/deletion RNA editing in mitochondrial mRNAs involves guide RNAs (gRNAs) and the auxiliary RNA editing substrate binding complex (RESC) and RNA editing helicase 2 complex (REH2C). RESC and REH2C stably copurify with editing mRNAs but the functional interplay between these complexes remains unclear. Most steady-state mRNAs are partially edited and include misedited “junction”

    更新日期:2020-11-16
  • In vitro studies provide insight into effects of Dicer-2 helicase mutations in Drosophila melanogaster.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Helen M Donelick,Loïc Talide,Matthieu Bellet,Joseph Aruscavage,Emilie Lauret,Eric Aguiar,João T Marques,Carine Meignin,Brenda L Bass

    In vitro, Drosophila melanogaster Dicer-2 (Dcr-2) uses its helicase domain to initiate processing of dsRNA with blunt (BLT) termini, and its Platform•PAZ domain to initiate processing of dsRNA with 3′ overhangs (ovrs). To understand the relationship of these in vitro observations to roles of Dcr-2 in vivo, we compared in vitro effects of two helicase mutations to their impact on production of endogenous

    更新日期:2020-11-16
  • A rare bacterial RNA motif is implicated in the regulation of the purF gene whose encoded enzyme synthesizes phosphoribosylamine.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Sarah Malkowski,Ruben Atilho,Etienne Greenlee,Christina Weinberg,Ronald R Breaker

    The Fibro-purF motif is a putative structured noncoding RNA domain that was discovered previously in species of Fibrobacter by using comparative sequence analysis methods. An updated bioinformatics search yielded a total of only 30 unique-sequence representatives, exclusively found upstream of the purF gene that codes for the enzyme amidophosphoribosyltransferase. This enzyme synthesizes the compound

    更新日期:2020-11-16
  • Processing of Alu small RNAs by DICER/ADAR1 complexes and their RNAi targets.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Yusuke Shiromoto,Masayuki Sakurai,Helen Qu,Andrew V Kossenkov,Kazuko Nishikura

    In addition to adenosine-to-inosine RNA editing activities, ADAR1 has been shown to have various RNA editing-independent activities including modulation of RNAi efficacy. We previously reported that ADAR1 forms a heterodimer complex with DICER and facilitates processing of pre-miRNAs to mature miRNAs. In addition to miRNA synthesis, DICER is involved in processing of long dsRNAs into small RNAs (endo-siRNAs)

    更新日期:2020-11-16
  • Phosphodiester modifications in mRNA polyA tail prevent deadenylation without compromising protein expression.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Dominika Strzelecka,Miroslaw Smietanski,Pawel Sikorski,Marcin Warminski,Joanna Kowalska,Jacek Jemielity

    Chemical modifications enable preparation of mRNAs with augmented stability and translational activity. In this study, we explored how chemical modifications of 5′,3′-phosphodiester bonds in the mRNA body and poly(A) tail influence the biological properties of eukaryotic mRNA. To obtain modified and unmodified in vitro transcribed mRNAs, we used ATP and ATP analogs modified at the α-phosphate (containing

    更新日期:2020-11-16
  • Folding heterogeneity in the essential human telomerase RNA three-way junction.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Christina Palka,Nicholas Forino,Jendrik Hentschel,Rhiju Das,Michael D Stone

    Telomeres safeguard the genome by suppressing illicit DNA damage responses at chromosome termini. To compensate for incomplete DNA replication at telomeres, most continually dividing cells, including many cancers, express the telomerase ribonucleoprotein (RNP) complex. Telomerase maintains telomere length by catalyzing de novo synthesis of short DNA repeats using an internal telomerase RNA (TR) template

    更新日期:2020-11-16
  • Human disease-associated single nucleotide polymorphism changes the orientation of DROSHA on pri-mir-146a
    RNA (IF 4.32) Pub Date : 2020-12-01
    Cong Truc Le; Thuy Linh Nguyen; Trung Duc Nguyen; Tuan Anh Nguyen

    The Microprocessor complex of DROSHA and DGCR8 initiates the biosynthesis of microRNAs (miRNAs) by processing primary miRNAs (pri-miRNAs). The Microprocessor can be oriented on pri-miRNAs in opposite directions to generate productive and unproductive cleavages at their basal and apical junctions, respectively. However, only the productive cleavage gives rise to miRNAs. A single nucleotide polymorphism

    更新日期:2020-11-16
  • The crystal structure of a Polerovirus exoribonuclease-resistant RNA shows how diverse sequences are integrated into a conserved fold.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Anna-Lena Steckelberg,Quentin Vicens,David A Costantino,Jay C Nix,Jeffrey S Kieft

    Exoribonuclease-resistant RNAs (xrRNAs) are discrete elements that block the progression of 5′ to 3′ exoribonucleases using specifically folded RNA structures. A recently discovered class of xrRNA is widespread in several genera of plant-infecting viruses, within both noncoding and protein-coding subgenomic RNAs. The structure of one such xrRNA from a dianthovirus revealed three-dimensional details

    更新日期:2020-11-16
  • Hierarchical Natural Move Monte Carlo Refines Flexible RNA Structures into Cryo-EM Densities.
    RNA (IF 4.32) Pub Date : 2020-12-01
    Jeng-Yih Chang,Zhicheng Cui,Kailu Yang,Jianhua Huang,Peter Minary,Junjie Zhang

    Ribonucleic acids (RNAs) play essential roles in living cells. Many of them fold into defined three-dimensional (3D) structures to perform functions. Recent advances in single-particle cryo-electron microscopy (cryo-EM) have enabled structure determinations of RNA to atomic resolutions. However, most RNA molecules are structurally flexible, limiting the resolution of their structures solved by cryo-EM

    更新日期:2020-11-16
  • Insertions of codons encoding basic amino acids in H7 hemagglutinins of influenza A viruses occur by recombination with RNA at hotspots near snoRNA binding sites
    RNA (IF 4.32) Pub Date : 2020-11-13
    Alexander P Gultyaev; Monique I Spronken; Mathis Funk; Ron A.M. Fouchier; Mathilde Richard

    The presence of multiple basic amino acids in the protease cleavage site of the hemagglutinin (HA) protein is the main molecular determinant of virulence of highly pathogenic avian influenza (HPAI) viruses. Recombination of HA RNA with other RNA molecules of host or virus origin is a dominant mechanism of multi basic cleavage site (MBCS) acquisition for H7 subtype HA. Using alignments of HA RNA sequences

    更新日期:2020-11-15
  • Expansion Segments in Bacterial and Archaeal 5S Ribosomal RNAs
    RNA (IF 4.32) Pub Date : 2020-11-12
    Victor G Stepanov; George E Fox

    The large ribosomal RNAs of eukaryotes frequently contain expansion sequences that add to the size of the rRNAs but do not affect their overall structural layout and are compatible with major ribosomal function as an mRNA translation machine. The expansion of prokaryotic ribosomal RNAs is much less explored. In order to obtain more insight into the structural variability of these conserved molecules

    更新日期:2020-11-13
  • Cold-inducible RNA binding protein promotes breast cancer cell malignancy by regulating Cystatin C levels
    RNA (IF 4.32) Pub Date : 2020-11-10
    Alberto Indacochea; Santiago Guerrero; Macarena Ureña; Ferran Araujo; Olga Coll; Matilde E LLeonart; Fatima Gebauer

    Cold-inducible RNA binding protein (CIRBP) is a stress-responsive protein that promotes cancer development and inflammation. Critical to most CIRBP functions is its capacity to bind and post-transcriptionally modulate mRNA. However, a transcriptome-wide analysis of CIRBP mRNA targets in cancer has not yet been performed. Here, we use an ex vivo breast cancer model to identify CIRBP targets and mechanisms

    更新日期:2020-11-12
  • Mechanistic analysis of the enhanced RNAi activity by 6-mCEPh-purine at the 5’ end of the siRNA guide strand
    RNA (IF 4.32) Pub Date : 2020-11-11
    Vincent Brechin; Fumikazu Shinohara; Jun-ichi Saito; Herve Seitz; Yukihide Tomari

    A key approach for improving siRNA efficacy is chemical modifications. Through an in-silico screening of modifications at the 5′-end nucleobase of the guide strand, an adenine-derived compound called 6-(3-(2-carboxyethyl)phenyl)-purine (6-mCEPh-purine) was identified to improve the RNAi activity in cultured human cells and in vivo mouse models. Nevertheless, it remains unclear how this chemical modification

    更新日期:2020-11-12
  • siRNA potency enhancement via chemical modifications of nucleotide bases at the 5′-end of the siRNA guide strand
    RNA (IF 4.32) Pub Date : 2020-11-11
    Fumikazu Shinohara; Taiji Oashi; Toshimasa Harumoto; Tomoyuki Nishikawa; Yuki Takayama; Hikaru Miyagi; Yuichi Takahashi; Takahiro Nakajima; Takashi Sawada; Yasuo Koda; Asana Makino; Atsuko Sato; Kaori Hamaguch; Michihiko Suzuki; Junichiro Yamamoto; Yukihide Tomari; Jun-Ichi Saito

    Small interfering RNAs (siRNAs) can be utilized not only as functional biological research tools but also as therapeutic agents. For the clinical use of siRNA as drugs, various chemical modifications have been employed to improve the activity of siRNA drugs, and further chemical modifications are expected to improve the utility of siRNA therapeutics. As the 5′ nucleobase of the guide strand affects

    更新日期:2020-11-12
  • Inducible nuclear import by TetR aptamer-controlled 3’ splice site selection
    RNA (IF 4.32) Pub Date : 2020-11-04
    Adam Mol; Marc Vogel; Beatrix Suess

    ABSTRACT Correct cellular localization is essential for the function of many eukaryotic proteins and hence cell physiology. Here, we present a synthetic genetic device that allows to control nuclear and cytosolic localization based on controlled alternative splicing in human cells. The device is based on the fact that an alternative 3’ splice site is located within a TetR aptamer that in turn is positioned

    更新日期:2020-11-04
  • PAR-TERRA is the main contributor to telomeric repeat-containing RNA transcripts in normal and cancer mouse cells
    RNA (IF 4.32) Pub Date : 2020-10-30
    Nikenza Viceconte; Axelle Loriot; Patricia Lona Abreu; Marion Scheibe; Albert Fradera Sola; Falk Butter; Charles De Smet; Claus M Azzalin; Nausica Arnoult; Anabelle Decottignies

    Telomeric repeat-containing RNA (TERRA) molecules play important roles at telomeres, from heterochromatin regulation to telomerase activity control. In human cells, TERRA is transcribed from subtelomeric promoters located on most chromosome ends and associates with telomeres. The origin of mouse TERRA molecules is however unclear, as transcription from the pseudoautosomal PAR locus was recently suggested

    更新日期:2020-11-02
  • A Second Riboswitch Class for the Enzyme Cofactor NAD+
    RNA (IF 4.32) Pub Date : 2020-10-21
    Shanker S.S. Panchapakesan; Lukas Corey; Sarah Malkowski; Gadareth Higgs; Ronald R Breaker

    A bacterial noncoding RNA motif almost exclusively associated with pnuC genes was uncovered using comparative sequence analysis. Some PnuC proteins are known to transport nicotinamide riboside (NR), which is a component of the ubiquitous and abundant enzyme cofactor nicotinamide adenine dinucleotide (NAD+). Thus, we speculated that the newly found ‘pnuC motif’ RNAs might function as aptamers for a

    更新日期:2020-10-29
  • A lncRNA-regulated gene expression system with rapid induction kinetics in the fission yeast Schizosaccharomyces pombe
    RNA (IF 4.32) Pub Date : 2020-11-01
    Angad Garg

    The fission yeast Schizosaccharomyces pombe is an excellent model organism for the study of eukaryotic cellular physiology. The organism is genetically tractable and several tools to study the functions of individual genes are available. One such tool is regulatable gene expression and overproduction of proteins. Limitations of currently available overexpression systems include delay in expression

    更新日期:2020-10-17
  • Ribo-Pop: simple, cost-effective, and widely applicable ribosomal RNA depletion
    RNA (IF 4.32) Pub Date : 2020-11-01
    Mary Kay Thompson; Maria Kiourlappou; Ilan Davis

    The measurement of RNA abundance derived from massively parallel sequencing experiments is an essential technique. Methods that reduce ribosomal RNA levels are usually required prior to sequencing library construction because ribosomal RNA typically comprises the vast majority of a total RNA sample. For some experiments, ribosomal RNA depletion is favored over poly(A) selection because it offers a

    更新日期:2020-10-17
  • Determination of primary microRNA processing in clinical samples by targeted pri-miR-sequencing
    RNA (IF 4.32) Pub Date : 2020-11-01
    Thomas Conrad; Evgenia Ntini; Benjamin Lang; Luca Cozzuto; Jesper B. Andersen; Jens U. Marquardt; Julia Ponomarenko; Gian Gaetano Tartaglia; Ulf A. Vang Ørom

    MicroRNA expression is important for gene regulation and deregulated microRNA expression is often observed in diseases such as cancer. The processing of primary microRNA transcripts is an important regulatory step in microRNA biogenesis. Due to low expression level and association with chromatin, primary microRNAs are challenging to study in clinical samples where input material is limited. Here, we

    更新日期:2020-10-17
  • The RNA transport factor PHAX is required for proper histone H2AX expression and DNA damage response
    RNA (IF 4.32) Pub Date : 2020-11-01
    Mitsuhiro Machitani; Ichiro Taniguchi; Asako McCloskey; Tatsuya Suzuki; Mutsuhito Ohno

    PHAX (phosphorylated adaptor for RNA export) promotes nuclear export of short transcripts of RNA polymerase II such as spliceosomal U snRNA precursors, as well as intranuclear transport of small nucleolar RNAs (snoRNAs). However, it remains unknown whether PHAX has other critical functions. Here we show that PHAX is required for efficient DNA damage response (DDR) via regulation of phosphorylated histone

    更新日期:2020-10-17
  • Contributions and competition of Mg2+ and K+ in folding and stabilization of the Twister ribozyme
    RNA (IF 4.32) Pub Date : 2020-11-01
    Abhishek A. Kognole; Alexander D. MacKerell, Jr.

    Native folded and compact intermediate states of RNA typically involve tertiary structures in the presence of divalent ions such as Mg2+ in a background of monovalent ions. In a recent study, we have shown how the presence of Mg2+ impacts the transition from partially unfolded to folded states through a “push-pull” mechanism where the ion both favors and disfavors the sampling of specific phosphate-phosphate

    更新日期:2020-10-17
  • Principles of mRNA control by human PUM proteins elucidated from multimodal experiments and integrative data analysis
    RNA (IF 4.32) Pub Date : 2020-11-01
    Michael B. Wolfe; Trista L. Schagat; Michelle T. Paulsen; Brian Magnuson; Mats Ljungman; Daeyoon Park; Chi Zhang; Zachary T. Campbell; Aaron C. Goldstrohm; Peter L. Freddolino

    The human PUF-family proteins, PUM1 and PUM2, posttranscriptionally regulate gene expression by binding to a PUM recognition element (PRE) in the 3′-UTR of target mRNAs. Hundreds of PUM1/2 targets have been identified from changes in steady-state RNA levels; however, prior studies could not differentiate between the contributions of changes in transcription and RNA decay rates. We applied metabolic

    更新日期:2020-10-17
  • 2′-fluoro-modified pyrimidines enhance affinity of RNA oligonucleotides to HIV-1 reverse transcriptase
    RNA (IF 4.32) Pub Date : 2020-11-01
    Paige R. Gruenke; Khalid K. Alam; Kamal Singh; Donald H. Burke

    Nucleic acid aptamers can be chemically modified to enhance function, but modifying previously selected aptamers can have nontrivial structural and functional consequences. We present a reselection strategy to evaluate the impact of several modifications on preexisting aptamer pools. RNA aptamer libraries with affinity to HIV-1 reverse transcriptase (RT) were retranscribed with 2′-F, 2′-OMe, or 2′-NH2

    更新日期:2020-10-17
  • Identification and rescue of a tRNA wobble inosine deficiency causing intellectual disability disorder
    RNA (IF 4.32) Pub Date : 2020-11-01
    Jillian Ramos; Melissa Proven; Jonatan Halvardson; Felix Hagelskamp; Ekaterina Kuchinskaya; Benjamin Phelan; Ryan Bell; Stefanie M. Kellner; Lars Feuk; Ann-Charlotte Thuresson; Dragony Fu

    The deamination of adenosine to inosine at the wobble position of tRNA is an essential post-transcriptional RNA modification required for wobble decoding in bacteria and eukaryotes. In humans, the wobble inosine modification is catalyzed by the heterodimeric ADAT2/3 complex. Here, we describe novel pathogenic ADAT3 variants impairing adenosine deaminase activity through a distinct mechanism that can

    更新日期:2020-10-17
  • PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses
    RNA (IF 4.32) Pub Date : 2020-11-01
    Andrés Di Paolo; Guillermo Eastman; Raquel Mesquita-Ribeiro; Joaquina Farias; Andrew Macklin; Thomas Kislinger; Nancy Colburn; David Munroe; José R. Sotelo Sosa; Federico Dajas-Bailador; José R. Sotelo-Silveira

    Programmed cell death 4 (PDCD4) protein is a tumor suppressor that inhibits translation through the mTOR-dependent initiation factor EIF4A, but its functional role and mRNA targets in neurons remain largely unknown. Our work identified that PDCD4 is highly expressed in axons and dendrites of CNS and PNS neurons. Using loss- and gain-of-function experiments in cortical and dorsal root ganglia primary

    更新日期:2020-10-17
  • 3′READS + RIP defines differential Staufen1 binding to alternative 3′UTR isoforms and reveals structures and sequence motifs influencing binding and polysome association
    RNA (IF 4.32) Pub Date : 2020-11-01
    Dinghai Zheng; Hana Cho; Wei Wang; Xavier Rambout; Bin Tian; Lynne E. Maquat

    Staufen1 (STAU1) is an RNA-binding protein (RBP) that interacts with double-stranded RNA structures and has been implicated in regulating different aspects of mRNA metabolism. Previous studies have indicated that STAU1 interacts extensively with RNA structures in coding regions (CDSs) and 3′-untranslated regions (3′UTRs). In particular, duplex structures formed within 3′UTRs by inverted-repeat Alu

    更新日期:2020-10-17
  • Antagonism between splicing and microprocessor complex dictates the serum-induced processing of lnc-MIRHG for efficient cell cycle reentry
    RNA (IF 4.32) Pub Date : 2020-11-01
    Qinyu Sun; Qinyu Hao; Yo-Chuen Lin; You Jin Song; Sushant Bangru; Waqar Arif; Vidisha Tripathi; Yang Zhang; Jung-Hyun Cho; Susan M. Freier; Lisa M. Jenkins; Jian Ma; Je-Hyun Yoon; Auinash Kalsotra; Ashish Lal; Supriya G. Prasanth; Kannanganattu V. Prasanth

    Cellular quiescence and cell cycle reentry regulate vital biological processes such as cellular development and tissue homeostasis and are controlled by precise regulation of gene expression. The roles of long noncoding RNAs (lncRNAs) during these processes remain to be elucidated. By performing genome-wide transcriptome analyses, we identify differential expression of several hundreds of lncRNAs,

    更新日期:2020-10-17
  • Structural basis of the interaction between cyclodipeptide synthases and aminoacylated tRNA substrates
    RNA (IF 4.32) Pub Date : 2020-11-01
    Gabrielle Bourgeois; Jérôme Seguin; Morgan Babin; Muriel Gondry; Yves Mechulam; Emmanuelle Schmitt

    Cyclodipeptide synthases (CDPSs) catalyze the synthesis of various cyclodipeptides by using two aminoacyl-tRNA (aa-tRNA) substrates in a sequential mechanism. Here, we studied binding of phenylalanyl-tRNAPhe to the CDPS from Candidatus Glomeribacter gigasporarum (Cglo-CDPS) by gel filtration and electrophoretic mobility shift assay. We determined the crystal structure of the Cglo-CDPS:Phe-tRNAPhe complex

    更新日期:2020-10-17
  • microRNA-seq of cartilage reveals an overabundance of miR-140-3p which contains functional isomiRs
    RNA (IF 4.32) Pub Date : 2020-11-01
    Steven Woods; Sarah Charlton; Kat Cheung; Yao Hao; Jamie Soul; Louise N. Reynard; Natalie Crowe; Tracey E. Swingler; Andrew J. Skelton; Katarzyna A. Piróg; Colin G. Miles; Dimitra Tsompani; Robert M. Jackson; Tamas Dalmay; Ian M. Clark; Matt J. Barter; David A. Young

    miR-140 is selectively expressed in cartilage. Deletion of the entire Mir140 locus in mice results in growth retardation and early-onset osteoarthritis-like pathology; however, the relative contribution of miR-140-5p or miR-140-3p to the phenotype remains to be determined. An unbiased small RNA sequencing approach identified miR-140-3p as significantly more abundant (>10-fold) than miR-140-5p in human

    更新日期:2020-10-17
  • The Thermus thermophilus DEAD-box protein Hera is a general RNA binding protein and plays a key role in tRNA metabolism
    RNA (IF 4.32) Pub Date : 2020-11-01
    Pascal Donsbach; Brian A. Yee; Dione Sanchez-Hevia; José Berenguer; Stefan Aigner; Gene W. Yeo; Dagmar Klostermeier

    RNA helicases catalyze the ATP-dependent destabilization of RNA duplexes. DEAD-box helicases share a helicase core that mediates ATP binding and hydrolysis, RNA binding and unwinding. Most members of this family contain domains flanking the core that can confer RNA substrate specificity and guide the helicase to a specific RNA. However, the in vivo RNA substrates of most helicases are currently not

    更新日期:2020-10-17
  • Impact of virus subtype and host IFNL4 genotype on large-scale RNA structure formation in the genome of hepatitis C virus
    RNA (IF 4.32) Pub Date : 2020-11-01
    Peter Simmonds; Lize Cuypers; Will L. Irving; John McLauchlan; Graham S. Cooke; Ellie Barnes; STOP-HCV Consortium; M. Azim Ansari; J. Ball; D. Bonsall; D. Brainard; G. Burgess; J. Dillon; G. Foster; C. Gore; N. Guha; R. Halford; K. Whitby; C. Holmes; A. Howe; E. Hudson; S. Hutchinson; S. Khakoo; P. Klenerman; N. Martin; B. Massetto; T. Mbisa; J. McHutchison; J. McKeating; A. Miners; A. Murray; P. Shaw;

    Mechanisms underlying the ability of hepatitis C virus (HCV) to establish persistent infections and induce progressive liver disease remain poorly understood. HCV is one of several positive-stranded RNA viruses capable of establishing persistence in their immunocompetent vertebrate hosts, an attribute previously associated with formation of large-scale RNA structure in their genomic RNA. We developed

    更新日期:2020-10-17
  • αβDCA method identifies unspecific binding but specific disruption of the group I intron by the StpA chaperone
    RNA (IF 4.32) Pub Date : 2020-11-01
    Vladimir Reinharz; Tsvi Tlusty

    Chaperone proteins—the most disordered among all protein groups—help RNAs fold into their functional structure by destabilizing misfolded configurations or stabilizing the functional ones. But disentangling the mechanism underlying RNA chaperoning is challenging, mostly because of inherent disorder of the chaperones and the transient nature of their interactions with RNA. In particular, it is unclear

    更新日期:2020-10-17
  • Unusual tertiary pairs in eukaryotic tRNAAla
    RNA (IF 4.32) Pub Date : 2020-11-01
    Eric Westhof; Shubo Liang; Xiaoling Tong; Xin Ding; Lu Zheng; Fangyin Dai

    tRNA molecules have well-defined sequence conservations that reflect the conserved tertiary pairs maintaining their architecture and functions during the translation processes. An analysis of aligned tRNA sequences present in the GtRNAdb database (the Lowe Laboratory, University of California, Santa Cruz) led to surprising conservations on some cytosolic tRNAs specific for alanine compared to other

    更新日期:2020-10-17
  • Viral subversion of nonsense-mediated mRNA decay
    RNA (IF 4.32) Pub Date : 2020-11-01
    Maximilian Wei-Lin Popp; Hana Cho; Lynne E. Maquat

    Viruses have evolved in tandem with the organisms that they infect. Afflictions of the plant and animal kingdoms with viral infections have forced the host organism to evolve new or exploit existing systems to develop the countermeasures needed to offset viral insults. As one example, nonsense-mediated mRNA decay, a cellular quality-control mechanism ensuring the translational fidelity of mRNA transcripts

    更新日期:2020-10-17
  • A systematic evaluation of bioinformatics tools for identification of long noncoding RNAs
    RNA (IF 4.32) Pub Date : 2020-10-14
    You Duan; Wanting Zhang; Yingyin Cheng; Mijuan Shi; Xiao-Qin Xia

    High-throughput RNA sequencing unveiled the complexity of transcriptome and significantly increased the records of long noncoding RNAs (lncRNAs) which were reported to participate in a variety of biological processes. Identification of lncRNAs is a key step of lncRNA analysis, and a bunch of bioinformatics tools have been developed for this purpose in recent years. While these tools allow us to identify

    更新日期:2020-10-14
  • The Virtual Circular Genome Model for Primordial RNA Replication
    RNA (IF 4.32) Pub Date : 2020-10-07
    Lijun Zhou; Dian Ding; Jack W. Szostak

    We propose a model for the replication of primordial protocell genomes that builds upon recent advances in the nonenzymatic copying of RNA. We suggest that the original genomes consisted of collections of oligonucleotides beginning and ending at all possible positions on both strands of one or more virtual circular sequences. Replication is driven by feeding with activated monomers and by the activation

    更新日期:2020-10-07
  • Understanding the characteristics of nonspecific binding of drug-like compounds to canonical stem-loop RNAs and their implications for functional cellular assays
    RNA (IF 4.32) Pub Date : 2020-10-07
    Megan L. Kelly; Chia-Chieh Chu; Honglue Shi; Laura R. Ganser; Hal P. Bogerd; Kelly Huynh; Yuze Hou; Bryan R. Cullen; Hashim M. Al-Hashimi

    Identifying small molecules that selectively bind an RNA target while discriminating against all other cellular RNAs is an important challenge in RNA-targeted drug discovery. Much effort has been directed toward identifying drug-like small molecules that minimize electrostatic and stacking interactions that lead to non-specific binding of aminoglycosides and intercalators to many stem-loop RNAs. Many

    更新日期:2020-10-07
  • Mammalian nuclear TRUB1, mitochondrial TRUB2 and cytoplasmic PUS10 produce conserved pseudouridine 55 in different sets of tRNA
    RNA (IF 4.32) Pub Date : 2020-10-06
    Shaoni Mukhopadhyay; Manisha Deogharia; Ramesh Gupta

    Most mammalian cytoplasmic tRNAs contain ribothymidine (T) and pseudouridine (Ψ) at positions 54 and 55, respectively. However, some tRNAs contain Ψ at both positions. Several Ψ54-containing tRNAs function as primers in retroviral DNA synthesis. The Ψ54 of these tRNAs is produced by PUS10, which can also synthesize Ψ55. Two other enzymes, TRUB1 and TRUB2 can also produce Ψ55. By nearest-neighbor analyses

    更新日期:2020-10-06
  • Mutations in Domain IV of Elongation Factor EF-G Confer -1 Frameshifting
    RNA (IF 4.32) Pub Date : 2020-10-02
    Dustin NIblett; Charlotte Nelson; Calvin S. Leung; Gillian Rexroad; Jake Cozy; Jie Zhou; Laura Lancaster; Harry F. Noller

    A recent crystal structure of a ribosome complex undergoing partial translocation in the absence of elongation factor EF-G showed disruption of codon-anticodon pairing and slippage of the reading frame by -1, directly implicating EF-G in preservation of the translational reading frame. Among mutations identified in a random screen for dominant-lethal mutations of EF-G were a cluster of 6 that map to

    更新日期:2020-10-04
  • Structural Diversity and Phylogenetic Distribution of Valyl tRNA-like Structures in Viruses
    RNA (IF 4.32) Pub Date : 2020-10-02
    Madeline E. Sherlock; Erik W. Hartwick; Andrea MacFadden; Jeffrey S. Kieft

    Viruses commonly use specifically folded RNA elements that interact with both host and viral proteins to perform functions important for diverse viral processes. Examples are found at the 3′ termini of certain positive-sense ssRNA virus genomes where they partially mimic tRNAs, including being aminoacylated by host cell enzymes. Valine-accepting tRNA-like structures (TLSVal) are an example that share

    更新日期:2020-10-02
  • Different tertiary interactions create the same important 3-D features in a distinct flavivirus xrRNA
    RNA (IF 4.32) Pub Date : 2020-10-01
    Rachel A. Jones; Anna-Lena Steckelberg; Quentin Vicens; Matthew J. Szucs; Benjamin M. Akiyama; Jeffrey S. Kieft

    During infection by a flavivirus (FV), cells accumulate noncoding subgenomic flavivirus RNAs (sfRNAs) that interfere with several antiviral pathways. These sfRNAs are formed by structured RNA elements in the 3′ untranslated region (UTR) of the viral genomic RNA, which block the progression of host cell exoribonucleases that have targeted the viral RNA. Previous work on these exoribonuclease-resistant

    更新日期:2020-10-02
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