Formation of the tRNA<sup>Lys</sup> packaging complex in HIV‐1

Kleiman, Lawrence; Jones, Christopher P.; Musier‐Forsyth, Karin

doi:10.1016/j.febslet.2009.11.038

Cited by 89 publications

(54 citation statements)

References 82 publications

(116 reference statements)

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“…38 This suggests a subsequent use of the mitochondrial LysRS in the cytoplasm of newly infected cells and, thus, a concomitant potential interaction with transcribed nuclear lookalikes of the mitochondrial Lys tRNA. Whether the virion-packaged LysRS participates in such an interaction or whether such an interaction has any relevance in the HIV infection cycle 39,40 are currently open questions.…”

Section: Mitochondrial Trna-lookalikes As a Potential Source Of Intacmentioning

confidence: 99%

Mitochondrial tRNA-lookalikes in nuclear chromosomes: Could they be functional?

2015

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The presence in human nuclear chromosomes of multiple sequences that are highly similar to human mitochondrial tRNAs (tRNA-lookalikes) raises intriguing questions about the possible functionality of these genomic loci. In this perspective, we explore the significance of the mitochondrial tRNA-lookalikes based on a series of properties that argue for their non-accidental nature. We particularly focus on the possibility of transcription as well as on potential functional roles for these sequences that can range from their acting as DNA regulatory elements to forming functional mature tRNAs or tRNA-derived fragments. Extension of our analysis to other simians (chimp, gorilla, rhesus, and squirrel monkey), 2 rodents (mouse and rat), a marsupial (opossum) and 3 invertebrates (fruit-fly, worm, and sponge) revealed that mitochondrial tRNA-lookalikes are prevalent in primates and the opossum but absent from the other analyzed organisms.

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Section: Mitochondrial Trna-lookalikes As a Potential Source Of Intacmentioning

confidence: 99%

Mitochondrial tRNA-lookalikes in nuclear chromosomes: Could they be functional?

2015

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“…Aside from providing stability to the aaRS–tRNA complex for aminoacylation directly, these additional RNA binding domains can be used to provide tRNA stability and even sometimes to facilitate transport. For example, cytoplasmic LysRS in humans is selectively packaged along with the tRNA Lys isoacceptors to help transport the tRNA Lys replication primer into the HIV-1 viron [237]. The viral Gag polyprotein is required for this packaging event.…”

Section: Functional Evolution Of Synthetasesmentioning

confidence: 99%

Emergence and Evolution

Bullwinkle

Ibba

2013

Topics in Current Chemistry

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The aminoacyl-tRNA synthetases (aaRSs) are essential components of the protein synthesis machinery responsible for defining the genetic code by pairing the correct amino acids to their cognate tRNAs. The aaRSs are an ancient enzyme family believed to have origins that may predate the last common ancestor and as such they provide insights into the evolution and development of the extant genetic code. Although the aaRSs have long been viewed as a highly conserved group of enzymes, findings within the last couple of decades have started to demonstrate how diverse and versatile these enzymes really are. Beyond their central role in translation, aaRSs and their numerous homologs have evolved a wide array of alternative functions both inside and outside translation. Current understanding of the emergence of the aaRSs, and their subsequent evolution into a functionally diverse enzyme family, are discussed in this chapter.

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“…The RNA genome contains a region known as the primer binding site (PBS), which is complementary to the 3= 18 nucleotides (nt) of a specific host cell tRNA that acts as a primer for reverse transcription (2). In human immunodeficiency virus type 1 (HIV-1), the primer is tRNA Lys3 (3,4), and in Rous sarcoma virus (RSV), it is tRNA Trp (5,6).…”

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confidence: 99%

Mechanistic Differences between Nucleic Acid Chaperone Activities of the Gag Proteins of Rous Sarcoma Virus and Human Immunodeficiency Virus Type 1 Are Attributed to the MA Domain

Rye-McCurdy

Nadaraia-Hoke

Gudleski-O'Regan

et al. 2014

J Virol

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Host cell tRNAs are recruited for use as primers to initiate reverse transcription in retroviruses. Human immunodeficiency virus type 1 (HIV-1) uses tRNALys3 as the replication primer, whereas Rous sarcoma virus (RSV) uses tRNA Trp . The nucleic acid (NA) chaperone function of the nucleocapsid (NC) domain of HIV-1 Gag is responsible for annealing tRNA Lys3 to the genomic RNA (gRNA) primer binding site (PBS). Compared to HIV-1, little is known about the chaperone activity of RSV Gag. In this work, using purified RSV Gag containing an N-terminal His tag and a deletion of the majority of the protease domain (H6.Gag.3h), gel shift assays were used to monitor the annealing of tRNA Trp to a PBS-containing RSV RNA. Here, we show that similar to HIV-1 Gag lacking the p6 domain (Gag⌬p6), RSV H6.Gag.3h is a more efficient chaperone on a molar basis than NC; however, in contrast to the HIV-1 system, both RSV H6.Gag.3h and NC have comparable annealing rates at protein saturation. The NC domain of RSV H6.Gag.3h is required for annealing, whereas deletion of the matrix (MA) domain, which stimulates the rate of HIV-1 Gag⌬p6 annealing, has little effect on RSV H6.Gag.3h chaperone function. Competition assays confirmed that RSV MA binds inositol phosphates (IPs), but in contrast to HIV-1 Gag⌬p6, IPs do not stimulate RSV H6.Gag.3h chaperone activity unless the MA domain is replaced with HIV-1 MA. We conclude that differences in the MA domains are primarily responsible for mechanistic differences in RSV and HIV-1 Gag NA chaperone function. IMPORTANCEMounting evidence suggests that the Gag polyprotein is responsible for annealing primer tRNAs to the PBS to initiate reverse transcription in retroviruses, but only HIV-1 Gag chaperone activity has been demonstrated in vitro. Understanding RSV Gag's NA chaperone function will allow us to determine whether there is a common mechanism among retroviruses. This report shows for the first time that full-length RSV Gag lacking the protease domain is a highly efficient NA chaperone in vitro, and NC is required for this activity. In contrast to results obtained for HIV-1 Gag, due to the weak nucleic acid binding affinity of the RSV MA domain, inositol phosphates do not regulate RSV Gag-facilitated tRNA annealing despite the fact that they bind to MA. These studies provide insight into the viral regulation of tRNA primer annealing, which is a potential target for antiretroviral therapy.

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Formation of the tRNA^Lys packaging complex in HIV‐1

Cited by 89 publications

References 82 publications

Mitochondrial tRNA-lookalikes in nuclear chromosomes: Could they be functional?

Mitochondrial tRNA-lookalikes in nuclear chromosomes: Could they be functional?

Emergence and Evolution

Mechanistic Differences between Nucleic Acid Chaperone Activities of the Gag Proteins of Rous Sarcoma Virus and Human Immunodeficiency Virus Type 1 Are Attributed to the MA Domain

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Formation of the tRNALys packaging complex in HIV‐1

Cited by 89 publications

References 82 publications

Mitochondrial tRNA-lookalikes in nuclear chromosomes: Could they be functional?

Mitochondrial tRNA-lookalikes in nuclear chromosomes: Could they be functional?

Emergence and Evolution

Mechanistic Differences between Nucleic Acid Chaperone Activities of the Gag Proteins of Rous Sarcoma Virus and Human Immunodeficiency Virus Type 1 Are Attributed to the MA Domain

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Formation of the tRNA^Lys packaging complex in HIV‐1