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      Cis-acting RNA elements in human and animal plus-strand RNA viruses

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          Abstract

          The RNA genomes of plus-strand RNA viruses have the ability to form secondary and higher-order structures that contribute to their stability and to their participation in inter- and intramolecular interactions. Those structures that are functionally important are called cis-acting RNA elements because their functions cannot be complemented in trans. They can be involved not only in RNA/RNA interactions but also in binding of viral and cellular proteins during the complex processes of translation, RNA replication and encapsidation. Most viral cis-acting RNA elements are located in the highly structured 5′- and 3′-nontranslated regions of the genomes but sometimes they also extend into the adjacent coding sequences. In addition, some cis-acting RNA elements are embedded within the coding sequences far away from the genomic ends. Although the functional importance of many of these structures has been confirmed by genetic and biochemical analyses, their precise roles are not yet fully understood. In this review we have summarized what is known about cis-acting RNA elements in nine families of human and animal plus-strand RNA viruses with an emphasis on the most thoroughly characterized virus families, the Picornaviridae and Flaviviridae.

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          The molecular biology of arteriviruses.

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            Frameshifting RNA pseudoknots: Structure and mechanism

            Programmed ribosomal frameshifting (PRF) is one of the multiple translational recoding processes that fundamentally alters triplet decoding of the messenger RNA by the elongating ribosome. The ability of the ribosome to change translational reading frames in the −1 direction (−1 PRF) is employed by many positive strand RNA viruses, including economically important plant viruses and many human pathogens, such as retroviruses, e.g., HIV-1, and coronaviruses, e.g., the causative agent of severe acute respiratory syndrome (SARS), in order to properly express their genomes. −1 PRF is programmed by a bipartite signal embedded in the mRNA and includes a heptanucleotide “slip site” over which the paused ribosome “backs up” by one nucleotide, and a downstream stimulatory element, either an RNA pseudoknot or a very stable RNA stem–loop. These two elements are separated by six to eight nucleotides, a distance that places the 5′ edge of the downstream stimulatory element in direct contact with the mRNA entry channel of the 30S ribosomal subunit. The precise mechanism by which the downstream RNA stimulates −1 PRF by the translocating ribosome remains unclear. This review summarizes the recent structural and biophysical studies of RNA pseudoknots and places this work in the context of our evolving mechanistic understanding of translation elongation. Support for the hypothesis that the downstream stimulatory element provides a kinetic barrier to the ribosome-mediated unfolding is discussed.
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              An efficient ribosomal frame-shifting signal in the polymerase-encoding region of the coronavirus IBV.

              The polymerase-encoding region of the genomic RNA of the coronavirus infectious bronchitis virus (IBV) contains two very large, briefly overlapping open reading frames (ORF), F1 and F2, and it has been suggested on the basis of sequence analysis that expression of the downstream ORF, F2, might be mediated through ribosomal frame-shifting. To examine this possibility a cDNA fragment containing the F1/F2 overlap region was cloned within a marker gene and placed under the control of the bacteriophage SP6 promoter in a recombinant plasmid. Messenger RNA transcribed from this plasmid, when translated in cell-free systems, specified the synthesis of polypeptides whose size was entirely consistent with the products predicted by an efficient ribosomal frame-shifting event within the overlap region. The nature of the products was confirmed by their reactivity with antisera raised against defined portions of the flanking marker gene. This is the first non-retroviral example of ribosomal frame-shifting in higher eukaryotes. Images Fig. 4. Fig. 6.
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                Author and article information

                Contributors
                Journal
                Biochim Biophys Acta Gene Regul Mech
                Biochim Biophys Acta Gene Regul Mech
                Biochimica et Biophysica Acta. Gene Regulatory Mechanisms
                Elsevier
                1874-9399
                1876-4320
                23 September 2009
                Sep-Oct 2009
                23 September 2009
                : 1789
                : 9
                : 495-517
                Affiliations
                Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY 11790, USA
                Author notes
                [* ]Corresponding author. Tel.: +1 631 632 9777; fax: +1 631 632 8891. apaul@ 123456notes.cc.sunysb.edu
                Article
                S1874-9399(09)00112-6
                10.1016/j.bbagrm.2009.09.007
                2783963
                19781674
                154706ab-e6fe-4a4e-925b-2138c3879b68
                Copyright © 2009 Elsevier B.V. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 4 June 2009
                : 9 September 2009
                : 13 September 2009
                Categories
                Article

                plus-strand rna virus,rna structure in plus-strand rna virus,ires element in picornavirus and other plus-strand rna virus,nontranslated region in plus-strand rna virus

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