Mechanism of ribosome shunting in <i>Rice tungro bacilliform pararetrovirus</i>

Pooggin, Mikhail M.; Ryabova, Lyubov A.; He, Xiaohua; Fütterer, Johannes; Höhn, Thomas

doi:10.1261/rna.2285806

Cited by 36 publications

(46 citation statements)

References 38 publications

(25 reference statements)

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“…The mechanism for expression of PB1-F2 product is not definitively known but is presumed to occur via ribosomal scanning (Chen et al 2001). RNA structure in this region may facilitate the initiation of translation at the PB1-F2 ORF as seen in other viruses with expressed internal ORFs (Ryabova and Hohn 2000;Pooggin et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Identification of potential conserved RNA secondary structure throughout influenza A coding regions

Moss¹,

Priore²,

Turner³

2011

RNA

163

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Influenza A is a negative sense RNA virus of significant public health concern. While much is understood about the life cycle of the virus, knowledge of RNA secondary structure in influenza A virus is sparse. Predictions of RNA secondary structure can focus experimental efforts. The present study analyzes coding regions of the eight viral genome segments in both the (+) and (-) sense RNA for conserved secondary structure. The predictions are based on identifying regions of unusual thermodynamic stabilities and are correlated with studies of suppression of synonymous codon usage (SSCU). The results indicate that secondary structure is favored in the (+) sense influenza RNA. Twenty regions with putative conserved RNA structure have been identified, including two previously described structured regions. Of these predictions, eight have high thermodynamic stability and SSCU, with five of these corresponding to current annotations (e.g., splice sites), while the remaining 12 are predicted by the thermodynamics alone. Secondary structures with high conservation of base-pairing are proposed within the five regions having known function. A combination of thermodynamics, amino acid and nucleotide sequence comparisons along with SSCU was essential for revealing potential secondary structures.

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Section: Discussionmentioning

confidence: 99%

Identification of potential conserved RNA secondary structure throughout influenza A coding regions

Moss¹,

Priore²,

Turner³

2011

RNA

163

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“…Unlike IRES-mediated translation, the 40S ribosomal subunit is recruited to the 5= end of the mRNA through a capdependent mechanism and commences scanning of the mRNA 5= UTR, sometimes translating a short open reading frame. The 40S subunit is then transferred from a shunt donor region to a shunt acceptor region, bypassing (without scanning) regions of the transcript to initiate translation at a downstream AUG. Ribosome shunting has been best characterized for cauliflower mosaic virus (CaMV), Sendai virus, rice tungro bacilliform virus, duck hepatitis B virus, and adenovirus (Ad) (23)(24)(25)(26)(27). The HSP70 and cIAP2 cellular mRNAs have also been shown to utilize a ribosome shunting mechanism (28,29).…”

mentioning

confidence: 99%

Ribosomal Protein S25 Dependency Reveals a Common Mechanism for Diverse Internal Ribosome Entry Sites and Ribosome Shunting

Hertz

Landry

Willis

et al. 2013

Molecular and Cellular Biology

129

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bDuring viral infection or cellular stress, cap-dependent translation is shut down. Proteins that are synthesized under these conditions use alternative mechanisms to initiate translation. This study demonstrates that at least two alternative translation initiation routes, internal ribosome entry site (IRES) initiation and ribosome shunting, rely on ribosomal protein S25 (RPS25). This suggests that they share a mechanism for initiation that is not employed by cap-dependent translation, since cap-dependent translation is not affected by the loss of RPS25. Furthermore, we demonstrate that viruses that utilize an IRES or a ribosome shunt, such as hepatitis C virus, poliovirus, or adenovirus, have impaired amplification in cells depleted of RPS25. In contrast, viral amplification of a virus that relies solely on cap-dependent translation, herpes simplex virus, is not hindered. We present a model that explains how RPS25 can be a nexus for multiple alternative translation initiation pathways.T he predominant translation initiation pathway for cellular mRNAs is cap dependent, which requires recognition of the mRNA 5= cap structure by the cap binding protein eukaryotic initiation factor 4E (eIF4E). eIF4E interacts with a complex of eukaryotic initiation factors to recruit the ribosome to the 5= end of the mRNA (1). However, some viral and cellular mRNAs contain an internal ribosome entry site (IRES) in their 5= untranslated region (UTR) that recruits the ribosome in a cap-independent manner. This allows translation of key regulatory proteins under conditions where cap-dependent translation is downregulated, such as during cell stress (2). In fact, 5 to 10% of cellular mRNAs have been predicted to contain IRES elements. IRESs are enriched in genes that encode proteins regulating growth, differentiation, and responses to stress (3, 4). Viruses have coopted this pathway by inhibiting cap-dependent translation and using an IRES to recruit host ribosomes to synthesize viral proteins (5).The mechanism of IRES-mediated translation is not well understood; however, our best understanding has come from studying viral IRESs. Viral IRESs have been characterized functionally according to the type and number of initiation factors required (6). The picornaviral IRESs require several canonical initiation factors and noncanonical IRES trans-acting factors (ITAFs) (6, 7). The hepatitis C virus (HCV) IRES can bind directly to the 40S ribosomal subunit but requires additional factors to initiate protein synthesis (8-10). The most streamlined IRESs are found in the intergenic region (IGR) of the Dicistroviridae virus family; they recruit the 40S and 60S subunits to form functional 80S complexes in the absence of any initiation factors (11-13).The IGR IRES binds to the intersubunit surface of the 40S subunit and occupies the peptidyl (P) and exit (E) sites, whereas the HCV IRES binds to the solvent side of the 40S subunit with only the finger-like domain IIb occupying the E site (14-16). While the binding of these two IRESs to the 40S subuni...

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“…Pol II-mediated transcription of the circular minichromosome generates a capped and polyadenylated pgRNA with terminal repeats which is transported to the cytoplasm for translation of viral proteins and subsequently for reverse transcription. As demonstrated for CaMV and Rice tungro bacilliform virus (RTBV; genus Tungrovirus), translation of pgRNA is initiated by a shunt mechanism in which ribosomes bypass a long leader sequence containing multiple short ORFs (sORFs) and folding into a stable stem-loop structure (33)(34)(35), both features conserved in plant pararetroviruses (36). Several consecutive viral ORFs on polycistronic pgRNA are then translated by reinitiation (CaMV) (37) or leaky-scanning (RTBV) (38) mechanisms.…”

mentioning

confidence: 99%

Evasion of Short Interfering RNA-Directed Antiviral Silencing in Musa acuminata Persistently Infected with Six Distinct Banana Streak Pararetroviruses

Rajeswaran

Séguin

Chabannes

et al. 2014

J Virol

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Vegetatively propagated crop plants often suffer from infections with persistent RNA and DNA viruses. Such viruses appear to evade the plant defenses that normally restrict viral replication and spread. The major antiviral defense mechanism is based on RNA silencing generating viral short interfering RNAs (siRNAs) that can potentially repress viral genes posttranscriptionally through RNA cleavage and transcriptionally through DNA cytosine methylation. Here we examined the RNA silencing machinery of banana plants persistently infected with six pararetroviruses after many years of vegetative propagation. Using deep sequencing, we reconstructed consensus master genomes of the viruses and characterized virus-derived and endogenous small RNAs. Consistent with the presence of endogenous siRNAs that can potentially establish and maintain DNA methylation, the banana genomic DNA was extensively methylated in both healthy and virus-infected plants. A novel class of abundant 20-nucleotide (nt) endogenous small RNAs with 5=-terminal guanosine was identified. In all virus-infected plants, 21-to 24-nt viral siRNAs accumulated at relatively high levels (up to 22% of the total small RNA population) and covered the entire circular viral DNA genomes in both orientations. The hotspots of 21-nt and 22-nt siRNAs occurred within open reading frame (ORF) I and II and the 5= portion of ORF III, while 24-nt siRNAs were more evenly distributed along the viral genome. Despite the presence of abundant viral siRNAs of different size classes, the viral DNA was largely free of cytosine methylation. Thus, the virus is able to evade siRNA-directed DNA methylation and thereby avoid transcriptional silencing. This evasion of silencing likely contributes to the persistence of pararetroviruses in banana plants. IMPORTANCEWe report that DNA pararetroviruses in Musa acuminata banana plants are able to evade DNA cytosine methylation and transcriptional gene silencing, despite being targeted by the host silencing machinery generating abundant 21-to 24-nucleotide short interfering RNAs. At the same time, the banana genomic DNA is extensively methylated in both healthy and virus-infected plants. Our findings shed light on the siRNA-generating gene silencing machinery of banana and provide a possible explanation why episomal pararetroviruses can persist in plants whereas true retroviruses with an obligatory genome-integration step in their replication cycle do not exist in plants. V iruses are often described as causing acute and persistent infections: acute virus infections cause severe disease symptoms and, in many cases, kill the host plant, whereas persistent virus infections normally cause mild symptoms and allow the host to recover from the disease; persistent virus infections can sometimes be beneficial for plant physiology (1). Depending on the environmental conditions and host plant species, the viral disease symptoms can oscillate from severe to nonvisible (recovery) and back. The molecular mechanisms underlying such oscillations in pers...

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Mechanism of ribosome shunting in Rice tungro bacilliform pararetrovirus

Cited by 36 publications

References 38 publications

Identification of potential conserved RNA secondary structure throughout influenza A coding regions

Identification of potential conserved RNA secondary structure throughout influenza A coding regions

Ribosomal Protein S25 Dependency Reveals a Common Mechanism for Diverse Internal Ribosome Entry Sites and Ribosome Shunting

Evasion of Short Interfering RNA-Directed Antiviral Silencing in Musa acuminata Persistently Infected with Six Distinct Banana Streak Pararetroviruses

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