Editorial Cite This: Biochemistry 2019, 58, 295−296
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Special Issue on Regulating the Central Dogma
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The complexity of the central dogma is underscored by the exquisite biochemistry of transfer RNA (tRNA), which is the key link in translating the genetic code into protein. Mario Mörl (Leipzip University) provides an insightful perspective on tRNA biology with a focus on the regulation of posttranscriptional tRNA processing. Valérie de Crécy-Lagard (University of Florida) provides an overview of the regulatory potential of tRNA modifications and their role in the cellular stress response. Jane Jackman (The Ohio State University) characterizes the mechanistic features of the SPOUT (SpoUTrmD) superfamily of SAM-dependent tRNA methyltransferases. A report from Jason Chin (Medical Research Council Laboratory of Molecular Biology) demonstrates that the recently identified pyrrolysyl-tRNA synthetase/tRNA pair from Methanomethylophilus alvus, which does not cross-react with the commonly used pyrrolysyl pair from Methanosarcina mazei, is active in mammalian cells and maintains the aforementioned lack of cross-reactivity. This discovery opens new possibilities for multisite noncanonical amino acid incorporation in mammalian cells. While the ability of the cell to chemically modify its genetic material is remarkable in itself, it also opens up exciting new avenues for the development of new technologies and therapeutics. A review co-authored by Nima Mosammaparast (Washington University in St. Louis) and John Tainer and Roopa Thapar (University of Texas M. D. Anderson Cancer Center) presents comprehensive summaries and novel perspectives on the reversible mechanisms of chemical modifications on DNA and RNA and its relation and potential directions to cancer research. A Perspective from Alexis Komor (University of California, San Diego) details the transformative power of base editing technology in chemically modifying the genetic code. Juewen Liu (University of Waterloo) describes the finding of a unique deoxyribozyme that uses iodine as a cofactor to process the cleavage of the phosphorothioate RNA bond. This discovery enabled the development of a catalytic beacon for biosensing of iodine. With the rapid advances of genomics and the development and availability of new physical tools in sequencing, imaging, and mass spectrometry, our knowledge of gene expression regulation has been growing at a rapid pace. Despite these advances, biochemistry remains an engine for new discovery and mechanistic illustration, as evidenced by the reports in this issue. Biochemists will continue to play key roles in future discoveries.
n the central dogma, genetic information is stored in DNA, transcribed into RNA, and then expressed into proteins that are responsible for most functional activities. Gene expression regulation occurs at multiple layers of transcription (DNA to RNA) and post-transcription events. For instance, the effects of epigenetic modifications in normal development and human diseases as well as the list of new modifications on DNA and histones have kept growing, suggesting additional pathways yet to be unveiled. In complex systems such as mammals, cellular levels of mRNA (mRNA) do not always correlate with protein expression. The localization, structure, modification, and bound proteins of specific mRNA can substantially alter protein expression. This special issue “Regulating the Central Dogma” includes new results, perspectives, and reviews from experts in the field that provide a broad view of multifaceted gene expression regulation. Several papers in this issue elucidate the complex mechanisms underlying the regulation of enzymatic machinery responsible for DNA and histone modifications. A review from Eva Nogales (University of California, Berkeley) examines the structural biology of the epigenetic silencing complex, Polycomb repressive complex 2 (PRC2). Vyacheslav Filichev, Elena Harjes (Massey University), and Daniel Harki (University of Minnesota) characterize different APOBEC proteins, which catalyze the deamination of cytidine in singlestranded DNA, and their interactions with short oligonucleotides containing cytidine nucleoside analogue 2′-deoxyzebularine. Rahul Kohli (University of Pennsylvania) reports a systematic investigation of the substrate preferences of the ten11 translocation (TET) enzymes, which catalyze the oxidation of 5mC in DNA and RNA. While epigenetic regulation in DNA and histone is wellknown, more recently modifications of RNA have emerged as significant and complex regulators of gene expression and cellular processes. A review from Matthias Soller (University of Birmingham) offers a comprehensive overview of the role of N6-methyladenosine (m6A), the most abundant modification on most eukaryotic mRNA, in gene regulation, with a focus on an evolutionary perspective of the modification. A Viewpoint from Kun Wang and Chengqi Yi (Peking University) explores the underlying mechanisms linking transcription and translation, highlighting the effect of the m6A modification on translation efficiency. Besides modifications, RNA structure and cellular localization are also critical in precise posttranscriptional gene expression regulation. Robert Spitale’s Perspective (University of California, Irvine) evaluates the currently available repertoire of biochemical methods for visualizing and analyzing RNA subcellular localization. Jens Kurreck (Technische Universität Berlin) offers a unique perspective on the regulation of gene expression by RNA Gquadruplexes. Ronald Breaker (Yale University) reports the most recent progress in discovering the ligands for the remarkable series of “ykkC” orphan riboswitch candidates, the majority of which have been shown to function as riboswitches for free guanidine. © 2019 American Chemical Society
Chuan He*
Department of Chemistry and Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, GCIS E319B, Chicago, Illinois 60637, United States Special Issue: Regulating the Central Dogma Received: January 22, 2019 Published: February 5, 2019 295
DOI: 10.1021/acs.biochem.9b00059 Biochemistry 2019, 58, 295−296
Biochemistry
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Editorial
AUTHOR INFORMATION
ORCID
Chuan He: 0000-0003-4319-7424 Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS.
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DOI: 10.1021/acs.biochem.9b00059 Biochemistry 2019, 58, 295−296
