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Journal Cover   Wiley Interdisciplinary Reviews : RNA
  [SJR: 5.014]   [H-I: 21]   [2 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Online) 1757-7012
   Published by John Wiley and Sons Homepage  [1598 journals]
  • Issue information
    • PubDate: 2015-08-18T14:34:16.353643-05:
      DOI: 10.1002/wrna.1298
  • Recombinant messenger RNA technology and its application in cancer
           immunotherapy, transcript replacement therapies, pluripotent stem cell
           induction, and beyond
    • Authors: Britta Vallazza; Sebastian Petri, Marco A. Poleganov, Florian Eberle, Andreas N. Kuhn, Ugur Sahin
      First page: 471
      Abstract: In recent years, the interest in using messenger RNA (mRNA) as a therapeutic means to tackle different diseases has enormously increased. This holds true not only for numerous preclinical studies, but mRNA has also entered the clinic to fight cancer. The advantages of using mRNA compared to DNA were recognized very early on, e.g., the lack of risk for genomic integration, or the expression of the encoded protein in the cytoplasm without the need to cross the nuclear membrane. However, it was generally assumed that mRNA is just not stable enough to give rise to sufficient expression of the encoded protein. Yet, an initially small group of mRNA aficionados could demonstrate that the stability of mRNA and the efficiency, by which the encoded protein is translated, can be significantly increased by selecting the right set of cis‐acting structural elements (including the 5′‐cap, 5′‐ and 3′‐untranslated regions, poly(A)‐tail, and modified building blocks). In parallel, significant advances in RNA packaging and delivery have been made, extending the potential for this molecule. This paved the way for further work to prove mRNA as a promising therapeutic for multiple diseases. Here, we review the developments to optimize mRNA regarding stability, translational efficiency, and immune‐modulating properties to enhance its functionality and efficacy as a therapeutic. Furthermore, we summarize the current status of preclinical and clinical studies that use mRNA for cancer immunotherapy, for the expression of functional proteins as so‐called transcript (or protein) replacement therapy, as well as for induction of pluripotent stem cells. For further resources related to this article, please visit the WIREs website. Conflict of interest: All authors are employees of BioNTech RNA Pharmaceuticals GmbH, a company that develops mRNA‐based therapeutics. In addition, ANK, FE, MAP, and US are inventors on patent applications, which cover distinct aspects of using mRNA as a therapeutic.
      PubDate: 2015-06-09T10:37:31.184321-05:
      DOI: 10.1002/wrna.1288
  • Post‐transcriptional regulation in corticogenesis: how
           RNA‐binding proteins help build the brain
    • First page: 501
      Abstract: The cerebral cortex, the brain structure responsible for our higher cognitive functions, is built during embryonic development in a process called corticogenesis. During corticogenesis, neural stem cells generate distinct populations of progenitors and excitatory neurons. These new neurons migrate radially in the cortex, eventually forming neuronal layers and establishing synaptic connections with other neurons both within and outside the cortex. Perturbations to corticogenesis can result in severe neurodevelopmental disorders, thus emphasizing the need to better understand molecular regulation of brain development. Recent studies in both model organisms and humans have collectively highlighted roles for post‐transcriptional regulation in virtually all steps of corticogenesis. Genomic approaches have revealed global RNA changes associated with spatial and temporal regulation of cortical development. Additionally, genetic studies have uncovered RNA‐binding proteins (RBPs) critical for cell proliferation, differentiation, and migration within the developing neocortex. Many of these same RBPs play causal roles in neurodevelopmental pathologies. In the developing neocortex, RBPs influence diverse steps of mRNA metabolism, including splicing, stability, translation, and localization. With the advent of new technologies, researchers have begun to uncover key transcripts regulated by these RBPs. Given the complexity of the developing mammalian cortex, a major challenge for the future will be to understand how dynamic RNA regulation occurs within heterogeneous cell populations, across space and time. In sum, post‐transcriptional regulation has emerged as a critical mechanism for driving corticogenesis and exciting direction of future research. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2015-06-18T13:50:56.287987-05:
      DOI: 10.1002/wrna.1289
  • The potential of the riboSNitch in personalized medicine
    • Authors: Amanda C. Solem; Matthew Halvorsen, Silvia B. V. Ramos, Alain Laederach
      First page: 517
      Abstract: RNA conformation plays a significant role in stability, ligand binding, transcription, and translation. Single nucleotide variants (SNVs) have the potential to disrupt specific structural elements because RNA folds in a sequence‐specific manner. A riboSNitch is an element of RNA structure with a specific function that is disrupted by an SNV or a single nucleotide polymorphism (SNP; or polymorphism; SNVs occur with low frequency in the population,
      PubDate: 2015-06-26T08:05:15.050672-05:
      DOI: 10.1002/wrna.1291
  • New insights into pri‐miRNA processing and accumulation in plants
    • Authors: Shuxin Zhang; Yuhui Liu, Bin Yu
      First page: 533
      Abstract: MicroRNAs (miRNAs) regulate many biological processes such as development, metabolism, and others. They are processed from their primary transcripts called primary miRNA transcripts (pri‐miRNAs) by the processor complex containing the RNAse III enzyme, DICER‐LIKE1 (DCL1), in plants. Consequently, miRNA biogenesis is controlled through altering pri‐miRNA accumulation and processing, which is crucial for plant development and adaptation to environmental changes. Plant pri‐miRNAs are transcribed by DNA‐dependent RNA polymerase II (Pol II) and their levels are determined through transcription and degradation, whereas pri‐miRNA processing is affected by its structure, splicing, alternative splicing, loading to the processor and the processor activity, which involve in many accessory proteins. Here, we summarize recent progresses related to pri‐miRNA transcription, stability, and processing in plants. For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.
      PubDate: 2015-06-29T04:06:39.600185-05:
      DOI: 10.1002/wrna.1292
  • On the path to genetic novelties: insights from programmed DNA elimination
           and RNA splicing
    • First page: 547
      Abstract: Understanding how genetic novelties arise is a central goal of evolutionary biology. To this end, programmed DNA elimination and RNA splicing deserve special consideration. While programmed DNA elimination reshapes genomes by eliminating chromatin during organismal development, RNA splicing rearranges genetic messages by removing intronic regions during transcription. Small RNAs help to mediate this class of sequence reorganization, which is not error‐free. It is this imperfection that makes programmed DNA elimination and RNA splicing excellent candidates for generating evolutionary novelties. Leveraging a number of these two processes' mechanistic and evolutionary properties, which have been uncovered over the past years, we present recently proposed models and empirical evidence for how splicing can shape the structure of protein‐coding genes in eukaryotes. We also chronicle a number of intriguing similarities between the processes of programmed DNA elimination and RNA splicing, and highlight the role that the variation in the population‐genetic environment may play in shaping their target sequences. For further resources related to this article, please visit the WIREs website.
      PubDate: 2015-07-03T04:59:27.222127-05:
      DOI: 10.1002/wrna.1293
  • Biogenesis, identification, and function of exonic circular RNAs
    • First page: 563
      Abstract: Circular RNAs (circRNAs) arise during post‐transcriptional processes, in which a single‐stranded RNA molecule forms a circle through covalent binding. Previously, circRNA products were often regarded to be splicing intermediates, by‐products, or products of aberrant splicing. But recently, rapid advances in high‐throughput RNA sequencing (RNA‐seq) for global investigation of nonco‐linear (NCL) RNAs, which comprised sequence segments that are topologically inconsistent with the reference genome, leads to renewed interest in this type of NCL RNA (i.e., circRNA), especially exonic circRNAs (ecircRNAs). Although the biogenesis and function of ecircRNAs are mostly unknown, some ecircRNAs are abundant, highly expressed, or evolutionarily conserved. Some ecircRNAs have been shown to affect microRNA regulation, and probably play roles in regulating parental gene transcription, cell proliferation, and RNA‐binding proteins, indicating their functional potential for development as diagnostic tools. To date, thousands of ecircRNAs have been identified in multiple tissues/cell types from diverse species, through analyses of RNA‐seq data. However, the detection of ecircRNA candidates involves several major challenges, including discrimination between ecircRNAs and other types of NCL RNAs (e.g., trans‐spliced RNAs and genetic rearrangements); removal of sequencing errors, alignment errors, and in vitro artifacts; and the reconciliation of heterogeneous results arising from the use of different bioinformatics methods or sequencing data generated under different treatments. Such challenges may severely hamper the understanding of ecircRNAs. Herein, we review the biogenesis, identification, properties, and function of ecircRNAs, and discuss some unanswered questions regarding ecircRNAs. We also evaluate the accuracy (in terms of sensitivity and precision) of some well‐known circRNA‐detecting methods. For further resources related to this article, please visit the WIREs website.
      PubDate: 2015-07-31T09:21:15.798867-05:
      DOI: 10.1002/wrna.1294
  • ‘Micro‐managers’ of hepatic lipid metabolism and NAFLD
    • Authors: Wei Liu; Hongchao Cao, Jun Yan, Ruimin Huang, Hao Ying
      First page: 581
      Abstract: Nonalcoholic fatty liver disease (NAFLD) is tightly associated with insulin resistance, type 2 diabetes, and obesity. As the defining feature of NAFLD, hepatic steatosis develops as a consequence of metabolic dysregulation of de novo lipogenesis, fatty acid uptake, fatty acid oxidation, and triglycerides (TG) export. MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs, play critical roles in various biological processes through regulating gene expression at post‐transcriptional level. A growing body of evidence suggests that miRNAs not only maintain hepatic TG homeostasis under physiological condition, but also participate in the pathogenesis of NAFLD. In this review, we focus on the current knowledge of the hepatic miRNAs associated with the development of liver steatosis and the regulatory mechanisms involved, which might be helpful to further understand the nature of NAFLD and provide a sound scientific basis for the drug development. For further resources related to this article, please visit the WIREs website.
      PubDate: 2015-07-21T14:51:27.591243-05:
      DOI: 10.1002/wrna.1295
  • Corrigendum
    • Pages: 595 - 596
      PubDate: 2015-08-18T14:34:22.558751-05:
      DOI: 10.1002/wrna.1299
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