Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of Programmed -1 Ribosomal Frameshifting

Wang, Xinlu; Xuan, Yi; Han, Yuling; Ding, Xiang; Yang, Kai; Yang, Fuquan; Gao, Pu; Goff, Stephen P.; Gao, Guangxia

doi:10.1016/j.cell.2018.12.030

Cited by 105 publications

(189 citation statements)

References 62 publications

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“…Recently, the -1PRF regulatory mechanism of HIV-1 is well elucidated. The host factor Shiftless is identified as an inhibitor of -1PRF, which interacts with -1PRF signal of HIV-1 mRNA and translating ribosomes and causes premature translation termination at the frameshifting site ( Figure 1F) [53]. In this process, translation release factor eRF1 and eRF3 are required, as well as eS31 (RPS27A) and uL5 (RPL11), which interact with Shiftless.…”

Section: Ribosome Shunting and Programmed -1 Ribosomal Frameshiftingmentioning

confidence: 99%

“…In this process, translation release factor eRF1 and eRF3 are required, as well as eS31 (RPS27A) and uL5 (RPL11), which interact with Shiftless. Upon the conformational rearrangements and intersubunit rotations, the two RPs respectively from 40S and 60S subunits join forces to sustain the association of Shiftless with the ribosome and viral RNA [53]. In yeast, RPL3, locating at the peptidyl transferase center, is responsible for translational fidelity of -1PRF ( Figure 1F), and the RPL3 mutations lead to rapid loss of M1 killer virus [54].…”

Section: Ribosome Shunting and Programmed -1 Ribosomal Frameshiftingmentioning

confidence: 99%

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Regulation of Ribosomal Proteins on Viral Infection

2019

Cells

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Ribosomal proteins (RPs), in conjunction with rRNA, are major components of ribosomes involved in the cellular process of protein biosynthesis, known as “translation”. The viruses, as the small infectious pathogens with limited genomes, must recruit a variety of host factors to survive and propagate, including RPs. At present, more and more information is available on the functional relationship between RPs and virus infection. This review focuses on advancements in my own understanding of critical roles of RPs in the life cycle of viruses. Various RPs interact with viral mRNA and proteins to participate in viral protein biosynthesis and regulate the replication and infection of virus in host cells. Most interactions are essential for viral translation and replication, which promote viral infection and accumulation, whereas the minority represents the defense signaling of host cells by activating immune pathway against virus. RPs provide a new platform for antiviral therapy development, however, at present, antiviral therapeutics with RPs involving in virus infection as targets is limited, and exploring antiviral strategy based on RPs will be the guides for further study.

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Section: Ribosome Shunting and Programmed -1 Ribosomal Frameshiftingmentioning

confidence: 99%

Section: Ribosome Shunting and Programmed -1 Ribosomal Frameshiftingmentioning

confidence: 99%

Regulation of Ribosomal Proteins on Viral Infection

2019

Cells

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“…The mRNA structure element stalls the ribosome, which facilitates slippage (14,92). -1PRF can be also facilitated by binding of miRNAs (86) or proteins (93)(94)(95)(96) to the sequence following the slippery site. Recent mechanistic studies suggested that despite the great variety of the frameshifting sequences, -1 frameshifting follows one of two main pathways (97-105) ( Figure 5).…”

Section: Spontaneous and Programmed Ribosome Frameshiftingmentioning

confidence: 99%

“…An intriguing example is the interferon-stimulated cellular protein Shiftless. -1PRF in retroviruses (HIV) and alphaviruses (SFV) seems to be suppressed by this protein, which is thought to bind to both the translating ribosome and the frameshifting mRNA motif by a mechanism that is not fully understood (93). Multiple attempts have been made to design synthetic drugs targeting the frameshifting motif of HIV-1 (121)(122)(123)(124)(125) and SARS coronavirus (126).…”

Section: Spontaneous and Programmed Ribosome Frameshiftingmentioning

confidence: 99%

Translational recoding: canonical translation mechanisms reinterpreted

Rodnina

Korniy

Klimova

et al. 2019

Nucleic Acids Research

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During canonical translation, the ribosome moves along an mRNA from the start to the stop codon in exact steps of one codon at a time. The collinearity of the mRNA and the protein sequence is essential for the quality of the cellular proteome. Spontaneous errors in decoding or translocation are rare and result in a deficient protein. However, dedicated recoding signals in the mRNA can reprogram the ribosome to read the message in alternative ways. This review summarizes the recent advances in understanding the mechanisms of three types of recoding events: stop-codon readthrough, -1 ribosome frameshifting and translational bypassing. Recoding events provide insights into alternative modes of ribosome dynamics that are potentially applicable to other non-canonical modes of prokaryotic and eukaryotic translation.

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“…4 Nevertheless, recent reports have also found that the efficiency of -1PRF can be tuned by regulatory proteins and/ or miRNA. [5][6][7] -1PRF is utilized to temporally and stoichiometrically regulate protein production during viral replication and assembly. For instance, the alphavirus structural proteins are most often produced from a single polyprotein that is cleaved into the capsid (CP), E3, E2, 6K, and E1 proteins ( Figure 1A).…”

Section: Introductionmentioning

confidence: 99%

Cotranslational Folding Stimulates Programmed Ribosomal Frameshifting in the Alphavirus Structural Polyprotein

Harrington

Zimmer

Chamness

et al. 2019

Preprint

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Viruses maximize their genetic coding capacity through a variety of biochemical mechanisms including programmed ribosomal frameshifting (PRF), which facilitates the production of multiple proteins from a single transcript. PRF is typically stimulated by structural elements within the mRNA that generate mechanical tension between the transcript and ribosome. However, in this work we show that the forces generated by the cotranslational folding of the nascent polypeptide chain can also enhance PRF. Using an array of biochemical, cellular, and computational techniques, we first demonstrate that the Sindbis virus structural polyprotein forms two competing topological isomers during biosynthesis at the ribosome-translocon complex. We then show that the formation of one of these topological isomers is linked to PRF. Coarse-grained molecular dynamic simulations reveal that the translocon-mediated membrane integration of a transmembrane domain upstream from the ribosomal slip-site generates a force on the nascent polypeptide chain that scales with observed frameshifting. Together, our results demonstrate that cotranslational folding of this protein generates a tension that stimulates PRF. To our knowledge, this constitutes the first example in which the conformational state of the nascent chain has been linked to PRF. These findings raise the possibility that, in addition to RNA-mediated translational recoding, a variety of cotranslational folding and/ or binding events may also stimulate PRF.

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Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of Programmed -1 Ribosomal Frameshifting

Cited by 105 publications

References 62 publications

Regulation of Ribosomal Proteins on Viral Infection

Regulation of Ribosomal Proteins on Viral Infection

Translational recoding: canonical translation mechanisms reinterpreted

Cotranslational Folding Stimulates Programmed Ribosomal Frameshifting in the Alphavirus Structural Polyprotein

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