scholarly journals The different pathways of HIV genomic RNA translation

2010 ◽  
Vol 38 (6) ◽  
pp. 1548-1552 ◽  
Author(s):  
Nathalie Chamond ◽  
Nicolas Locker ◽  
Bruno Sargueil
Keyword(s):  
Rna Structure ◽  
Genomic Rna ◽  
Coding Region ◽  
Structural Determinants ◽  
Initiation Complex ◽  
Internal Ribosome Entry ◽  
Genomic Rnas ◽  
Initiation Factors ◽  
Rna Domains ◽  
And Function

Lentiviruses, the prototype of which is HIV-1, can initiate translation either by the classical cap-dependent mechanism or by internal recruitment of the ribosome through RNA domains called IRESs (internal ribosome entry sites). Depending on the virus considered, the mechanism of IRES-dependent translation differs widely. It can occur by direct binding of the 40S subunit to the mRNA, necessitating a subset or most of the canonical initiation factors and/or ITAF (IRES trans-acting factors). Nonetheless, a common feature of IRESs is that ribosomal recruitment relies, at least in part, on IRES structural determinants. Lentiviral genomic RNAs present an additional level of complexity, as, in addition to the 5′-UTR (untranslated region) IRES, the presence of a new type of IRES, embedded within Gag coding region was described recently. This IRES, conserved in all three lentiviruses examined, presents conserved structural motifs that are crucial for its activity, thus reinforcing the link between RNA structure and function. However, there are still important gaps in our understanding of the molecular mechanism underlying IRES-dependent translation initiation of HIV, including the determination of the initiation factors required, the dynamics of initiation complex assembly and the dynamics of the RNA structure during initiation complex formation. Finally, the ability of HIV genomic RNA to initiate translation through different pathways questions the possible mechanisms of regulation and their correlation to the viral paradigm, i.e. translation versus encapsidation of its genomic RNA.

scholarly journals Structures and Functions of Viral 5′ Non-Coding Genomic RNA Domain-I in Group-B Enterovirus Infections

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 919 ◽  
Author(s):  
Marie Glenet ◽  
Laetitia Heng ◽  
Domitille Callon ◽  
Anne-Laure Lebreil ◽  
Paul-Antoine Gretteau ◽  
...  
Keyword(s):  
Viral Replication ◽  
Secondary Structures ◽  
Genomic Rna ◽  
Coding Region ◽  
Entry Site ◽  
Rna Domains ◽  
Group B ◽  
Human Infections ◽  
Domain I

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5′ end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (internal ribosome entry site, IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5′ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I (Retinoic acid inducible gene I) or MDA5 (melanoma differentiation-associated protein 5) receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host–cell interactions driving the development of acute or persistent EV-B infections.

Lentiviral RNAs can use different mechanisms for translation initiation

2008 ◽  
Vol 36 (4) ◽  
pp. 690-693 ◽  
Author(s):  
Emiliano P. Ricci ◽  
Ricardo Soto Rifo ◽  
Cécile H. Herbreteau ◽  
Didier Decimo ◽  
Théophile Ohlmann
Keyword(s):  
Genomic Rna ◽  
Coding Region ◽  
Entry Site ◽  
Rna Motifs ◽  
Internal Ribosome Entry ◽  
Gag Polyprotein ◽  
Immunodeficiency Virus ◽  
Reticulocyte Lysate ◽  
Hiv 1 ◽  
Dependent Mechanism

The full-length genomic RNA of lentiviruses can be translated to produce proteins and incorporated as genomic RNA in the viral particle. Interestingly, both functions are driven by the genomic 5′-UTR (5′-untranslated region), which harbours structural RNA motifs for the replication cycle of the virus. Recent work has shown that this RNA architecture also functions as an IRES (internal ribosome entry site) in HIV-1 and -2, and in SIV (simian immunodeficiency virus). In addition, the IRES extends to the gag coding region for all these viruses and this leads to the synthesis of shorter isoforms of the Gag polyprotein from downstream initiation codons. In the present study, we have investigated how different members of the lentivirus family (namely HIV-1 and -2, and SIV) can initiate protein synthesis by distinct mechanisms. For this, we have used the competitive reticulocyte lysate that we have recently described. Our results show that HIV-1 is able to drive the synthesis of the Gag polyprotein both by a classical cap-dependent mechanism and an IRES, whereas HIV-2 and SIV appear to use exclusively an IRES mechanism.

scholarly journals Structures and Functions of Viral 5’ Non-Coding Genomic RNA Domain-I in Enterovirus-B Infections

2020 ◽  
Author(s):  
Marie GLENET ◽  
Laetitia HENG ◽  
Domitille CALLON ◽  
Anne-Laure LEBREIL ◽  
Paul-Antoine GRETTEAU ◽  
...  
Keyword(s):  
Viral Replication ◽  
Secondary Structures ◽  
Genomic Rna ◽  
Coding Region ◽  
Viral Genomes ◽  
Rna Domains ◽  
Group B ◽  
Human Infections ◽  
Domain I

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5'end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5’ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I or MDA5 receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host-cell interactions driving the development of acute or persistent EV-B infections.

scholarly journals A mechanism for ligand gated strand displacement in ZTP riboswitch transcription regulation

2019 ◽  
Author(s):  
Eric J. Strobel ◽  
Luyi Cheng ◽  
Katherine E. Berman ◽  
Paul D. Carlson ◽  
Julius B. Lucks
Keyword(s):  
Rna Structure ◽  
Clostridium Beijerinckii ◽  
Strand Displacement ◽  
Structural Determinants ◽  
Rna Molecules ◽  
Guide Rna ◽  
Folding Pathways ◽  
Rna Biogenesis ◽  
And Function ◽  
Downstream Gene Expression

AbstractCotranscriptional folding is an obligate step of RNA biogenesis that can guide RNA structure and function by forming transient intermediate folds. This is especially true for transcriptional riboswitches in the which the formation of ligand-dependent structures during transcription regulates downstream gene expression. However, the intermediate structures that comprise cotranscriptional RNA folding pathways and the mechanisms that enable transit between them remain largely unknown. Here we determine the series of cotranscriptional folds and rearrangements that mediate antitermination by the Clostridium beijerinckii pfl riboswitch in response to the purine biosynthetic intermediate ZMP. We uncover sequence and structural determinants that modulate a regulatory RNA strand displacement reaction and identify biases within natural ZTP riboswitch sequences that promote on-pathway folding. Our findings establish a mechanism for ZTP riboswitch antitermination and suggest general strategies by which nascent RNA molecules can navigate cotranscriptional folding pathways efficiently.

scholarly journals Specific Recognition of a Stem-Loop RNA Structure by the Alphavirus Capsid Protein

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1517
Author(s):  
Rebecca S. Brown ◽  
Lisa Kim ◽  
Margaret Kielian
Keyword(s):  
Capsid Protein ◽  
Rna Structure ◽  
Semliki Forest Virus ◽  
Virus Assembly ◽  
Specific Binding ◽  
Genomic Rna ◽  
Stem Loop ◽  
Stem Loop Structure ◽  
Labeled Rna

Alphaviruses are small enveloped viruses with positive-sense RNA genomes. During infection, the alphavirus capsid protein (Cp) selectively packages and assembles with the viral genomic RNA to form the nucleocapsid core, a process critical to the production of infectious virus. Prior studies of the alphavirus Semliki Forest virus (SFV) showed that packaging and assembly are promoted by Cp binding to multiple high affinity sites on the genomic RNA. Here, we developed an in vitro Cp binding assay based on fluorescently labeled RNA oligos. We used this assay to explore the RNA sequence and structure requirements for Cp binding to site #1, the top binding site identified on the genomic RNA during all stages of virus assembly. Our results identify a stem-loop structure that promotes specific binding of the SFV Cp to site #1 RNA. This structure is also recognized by the Cps of the related alphaviruses chikungunya virus and Ross River virus.

scholarly journals mRNA Molecules Containing Murine Leukemia Virus Packaging Signals Are Encapsidated as Dimers

2004 ◽  
Vol 78 (20) ◽  
pp. 10927-10938 ◽  
Author(s):  
Catherine S. Hibbert ◽  
Jane Mirro ◽  
Alan Rein
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Genomic Rna ◽  
Packaging Signal ◽  
Electron Microscopic ◽  
Genomic Rnas ◽  
Microscopic Studies ◽  
The Stability ◽  
Murine Leukemia

ABSTRACT Prior work by others has shown that insertion of ψ (i.e., leader) sequences from the Moloney murine leukemia virus (MLV) genome into the 3′ untranslated region of a nonviral mRNA leads to the specific encapsidation of this RNA in MLV particles. We now report that these RNAs are, like genomic RNAs, encapsidated as dimers. These dimers have the same thermostability as MLV genomic RNA dimers; like them, these dimers are more stable if isolated from mature virions than from immature virions. We characterized encapsidated mRNAs containing deletions or truncations of MLV ψ or with ψ sequences from MLV-related acute transforming viruses. The results indicate that the dimeric linkage in genomic RNA can be completely attributed to the ψ region of the genome. While this conclusion agrees with earlier electron microscopic studies on mature MLV dimers, it is the first evidence as to the site of the linkage in immature dimers for any retrovirus. Since the Ψ+ mRNA is not encapsidated as well as genomic RNA, it is only present in a minority of virions. The fact that it is nevertheless dimeric argues strongly that two of these molecules are packaged into particles together. We also found that the kissing loop is unnecessary for this coencapsidation or for the stability of mature dimers but makes a major contribution to the stability of immature dimers. Our results are consistent with the hypothesis that the packaging signal involves a dimeric structure in which the RNAs are joined by intermolecular interactions between GACG loops.

scholarly journals ATP-dependent unwinding of messenger RNA structure by eukaryotic initiation factors.

1985 ◽  
Vol 260 (12) ◽  
pp. 7651-7658 ◽  
Author(s):  
B K Ray ◽  
T G Lawson ◽  
J C Kramer ◽  
M H Cladaras ◽  
J A Grifo ◽  
...  
Keyword(s):  
Rna Structure ◽  
Messenger Rna ◽  
Initiation Factors ◽  
Eukaryotic Initiation Factors

scholarly journals Stem–loop formation drives RNA folding in mechanical unzipping experiments

2022 ◽  
Vol 119 (3) ◽  
pp. e2025575119
Author(s):  
Paolo Rissone ◽  
Cristiano V. Bizarro ◽  
Felix Ritort
Keyword(s):  
Optical Tweezers ◽  
Rna Structure ◽  
Nearest Neighbor ◽  
Rna Folding ◽  
General Mechanism ◽  
Loop Formation ◽  
Stem Loop ◽  
Wide Range ◽  
Irreversible Effects ◽  
And Function

Accurate knowledge of RNA hybridization is essential for understanding RNA structure and function. Here we mechanically unzip and rezip a 2-kbp RNA hairpin and derive the 10 nearest-neighbor base pair (NNBP) RNA free energies in sodium and magnesium with 0.1 kcal/mol precision using optical tweezers. Notably, force–distance curves (FDCs) exhibit strong irreversible effects with hysteresis and several intermediates, precluding the extraction of the NNBP energies with currently available methods. The combination of a suitable RNA synthesis with a tailored pulling protocol allowed us to obtain the fully reversible FDCs necessary to derive the NNBP energies. We demonstrate the equivalence of sodium and magnesium free-energy salt corrections at the level of individual NNBP. To characterize the irreversibility of the unzipping–rezipping process, we introduce a barrier energy landscape of the stem–loop structures forming along the complementary strands, which compete against the formation of the native hairpin. This landscape correlates with the hysteresis observed along the FDCs. RNA sequence analysis shows that base stacking and base pairing stabilize the stem–loops that kinetically trap the long-lived intermediates observed in the FDC. Stem–loops formation appears as a general mechanism to explain a wide range of behaviors observed in RNA folding.

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