scholarly journals HIV-1: To Splice or Not to Splice, That Is the Question

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 181
Author(s):  
Ann Emery ◽  
Ronald Swanstrom
Keyword(s):  
Full Length ◽  
Regulatory Sequences ◽  
Supporting Evidence ◽  
Control Mechanisms ◽  
Genomic Rna ◽  
Cis Acting ◽  
Splicing Regulators ◽  
Individual Transcript ◽  
Mrna Transcripts ◽  
Hiv 1

The transcription of the HIV-1 provirus results in only one type of transcript—full length genomic RNA. To make the mRNA transcripts for the accessory proteins Tat and Rev, the genomic RNA must completely splice. The mRNA transcripts for Vif, Vpr, and Env must undergo splicing but not completely. Genomic RNA (which also functions as mRNA for the Gag and Gag/Pro/Pol precursor polyproteins) must not splice at all. HIV-1 can tolerate a surprising range in the relative abundance of individual transcript types, and a surprising amount of aberrant and even odd splicing; however, it must not over-splice, which results in the loss of full-length genomic RNA and has a dramatic fitness cost. Cells typically do not tolerate unspliced/incompletely spliced transcripts, so HIV-1 must circumvent this cell policing mechanism to allow some splicing while suppressing most. Splicing is controlled by RNA secondary structure, cis-acting regulatory sequences which bind splicing factors, and the viral protein Rev. There is still much work to be done to clarify the combinatorial effects of these splicing regulators. These control mechanisms represent attractive targets to induce over-splicing as an antiviral strategy. Finally, splicing has been implicated in latency, but to date there is little supporting evidence for such a mechanism. In this review we apply what is known of cellular splicing to understand splicing in HIV-1, and present data from our newer and more sensitive deep sequencing assays quantifying the different HIV-1 transcript types.

scholarly journals HIV- 1:  To Splice Or Not To Splice, That Is THE Question

2021 ◽  
Author(s):  
Ronald Swanstrom ◽  
Ann Emery
Keyword(s):  
Fitness Cost ◽  
Full Length ◽  
Regulatory Sequences ◽  
Supporting Evidence ◽  
Control Mechanisms ◽  
Genomic Rna ◽  
Cis Acting ◽  
Splicing Regulators ◽  
Mrna Transcripts ◽  
Hiv 1

HIV-1 transcribes only one kind of transcript – the full length genomic RNA. To make the mRNA transcripts for the accessory proteins Tat and Rev, the genomic RNA must completely splice. The mRNA transcripts for Vif, Vpr, and Env must splice but not completely.  Genomic RNA (which also functions as mRNA for the Gag and Gag/Pro/Pol precursor polyproteins) must not splice at all.  HIV-1 can tolerate a surprising range in the relative abundance of individual transcript types, and a surprising amount of aberrant and even odd splicing; however, it must not over-splice, which results in the loss of full length genomic RNA and has a dramatic fitness cost.  Loss of full length genomic transcripts through over-splicing has a dramatic fitness cost.  Cells typically do not tolerate unspliced/incompletely spliced transcripts, so HIV-1 has to circumvent this cell policing mechanism to allow some splicing while suppressing most.  Splicing is controlled by RNA secondary structure, cis-acting regulatory sequences which bind splicing factors, and the viral protein Rev.  There is still much work to be done to clarify the combinatorial effects of these splicing regulators.  These control mechanisms represent attractive targets to induce over-splicing as an antiviral strategy. Finally, splicing has been implicated in latency, but to date there is little supporting evidence for such a mechanism. In this review we apply what is known of cellular splicing to understand splicing in HIV-1, and also present data from our newer and more sensitive deep sequencing assays quantifying the different HIV-1 transcript types.

scholarly journals Tomato Bushy Stunt Virus Genomic RNA Accumulation Is Regulated by Interdependent cis-Acting Elements within the Movement Protein Open Reading Frames

2002 ◽  
Vol 76 (24) ◽  
pp. 12747-12757 ◽  
Author(s):  
Jong-Won Park ◽  
Bénédicte Desvoyes ◽  
Herman B. Scholthof
Keyword(s):  
Movement Protein ◽  
Regulatory Element ◽  
Inhibitory Effect ◽  
Tomato Bushy Stunt Virus ◽  
Open Reading Frames ◽  
Regulatory Sequences ◽  
Genomic Rna ◽  
Cis Acting ◽  
Hairpin Loops ◽  
Rna Accumulation

ABSTRACT This study on Tomato bushy stunt virus identified and defined three previously unknown regulatory sequences involved in RNA accumulation that are located within the 3′-proximal nested movement protein genes p22 and p19. The first is a 16-nucleotide (nt) element termed III-A that is positioned at the very 3′ end of p22 and is essential for RNA accumulation. Approximately 300 nt upstream of III-A resides an ∼80-nt inhibitory element (IE) that is obstructive to replication only in the absence of a third regulatory element of ∼30 nt (SUR-III) that is positioned immediately upstream of III-A. Inspection of the nucleotide sequences predicted that III-A and SUR-III can form looped hairpins. A comparison of different tombusviruses showed, in each case, conservation for potential base pairing between the two predicted hairpin-loops. Insertion of a spacer adjacent to the predicted hairpins had no or a minimal effect on RNA accumulation, whereas an insertion in the putative III-A loop abolished genomic RNA multiplication. We conclude that the sequences composing the predicted III-A and SUR-III hairpin-loops are crucial for optimal RNA accumulation and that the inhibitory effect of IE surfaces when the alleged interaction between SUR-III and III-A is disturbed.

scholarly journals An epitranscriptomic switch at the 5′-UTR controls genome selection during HIV-1 genomic RNA packaging

2019 ◽  
Author(s):  
Camila Pereira-Montecinos ◽  
Daniela Toro-Ascuy ◽  
Cecilia Rojas-Fuentes ◽  
Sebastián Riquelme-Barrios ◽  
Bárbara Rojas-Araya ◽  
...  
Keyword(s):  
Full Length ◽  
Genomic Rna ◽  
Rna Packaging ◽  
Gag Protein ◽  
Rna Molecules ◽  
Viral Genomes ◽  
Viral Particles ◽  
Demethylase Activity ◽  
Retroviral Replication ◽  
Hiv 1

ABSTRACTDuring retroviral replication, the full-length RNA serves both as mRNA and genomic RNA (gRNA). While the simple retrovirus MLV segregates its full-length RNA into two functional populations, the HIV-1 full-length RNA was proposed to exist as a single population used indistinctly for protein synthesis or packaging. However, the mechanisms by which the HIV-1 Gag protein selects the two RNA molecules that will be packaged into nascent virions remain poorly understood. Here, we demonstrate that HIV-1 full-length RNA packaging is regulated through an epitranscriptomic switch requiring demethylation of two conserved adenosine residues present within the 5′-UTR. As such, while m6A deposition by METTL3/METTL14 onto the full-length RNA was associated with increased Gag synthesis and reduced packaging, FTO-mediated demethylation was required for the incorporation of the full-length RNA into viral particles. Interestingly, HIV-1 Gag associates with the RNA demethylase FTO in the nucleus and drives full-length RNA demethylation. Finally, the specific inhibition of the FTO RNA demethylase activity suppressed HIV-1 full-length RNA packaging. Together, our data propose a novel epitranscriptomic mechanism allowing the selection of the full-length RNA molecules that will be used as viral genomes.

Modeling the dynamics of the solvated SL1 domain of HIV-1 genomic RNA

Biopolymers ◽  
2003 ◽  
Vol 69 (1) ◽  
pp. 1-14 ◽  
Author(s):  
G. La Penna ◽  
D. Genest ◽  
A. Perico
Keyword(s):  
Genomic Rna ◽  
Hiv 1

HIV-1 mRNA Transcripts from Persistently Infected Human Fetal Astrocytes

1993 ◽  
Vol 693 (1 Pediatric AID) ◽  
pp. 324-326 ◽  
Author(s):  
WALTER J. ATWOOD ◽  
CARLO S. TORNATORE ◽  
KAREN MEYERS ◽  
EUGENE O. MAJOR
Keyword(s):  
Persistently Infected ◽  
Mrna Transcripts ◽  
Hiv 1

trans-Activation of the HIV-1 LTR by the HIV-1 tat and HTLV-I tax proteins is mediated by different cis-acting sequences

Virology ◽  
1991 ◽  
Vol 182 (2) ◽  
pp. 874-878 ◽  
Author(s):  
Klaus Zimmermann ◽  
Marika Dobrovnik ◽  
Claudia Ballaun ◽  
Dorian Bevec ◽  
Joachim Hauber ◽  
...  
Keyword(s):  
Cis Acting ◽  
Hiv 1

scholarly journals Substance P enhances HIV-1 infection in human fetal brain cell cultures expressing full-length neurokinin-1 receptor

2013 ◽  
Vol 19 (3) ◽  
pp. 219-227 ◽  
Author(s):  
Lynnae Schwartz ◽  
Sergei V. Spitsin ◽  
John Meshki ◽  
Florin Tuluc ◽  
Steven D. Douglas ◽  
...  
Keyword(s):  
Substance P ◽  
Cell Cultures ◽  
Fetal Brain ◽  
Brain Cell ◽  
Full Length ◽  
Human Fetal Brain ◽  
Neurokinin 1 Receptor ◽  
Brain Cell Cultures ◽  
Neurokinin 1 ◽  
Hiv 1

Tracing the origin and history of HIV-1 subtype B′ epidemic by near full-length genome analyses

AIDS ◽  
2012 ◽  
Vol 26 (7) ◽  
pp. 877-884 ◽  
Author(s):  
Zhe Li ◽  
Xiang He ◽  
Zhe Wang ◽  
Hui Xing ◽  
Fan Li ◽  
...  
Keyword(s):  
Full Length ◽  
Subtype B ◽  
History Of ◽  
Genome Analyses ◽  
Full Length Genome ◽  
Hiv 1

Reconstitution of the vitamin D-responsive osteocalcin transcription unit in Saccharomyces cerevisiae

1989 ◽  
Vol 9 (8) ◽  
pp. 3517-3523
Author(s):  
D P McDonnell ◽  
J W Pike ◽  
D J Drutz ◽  
T R Butt ◽  
B W O'Malley
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Vitamin D ◽  
Transcription Factors ◽  
Promoter Activity ◽  
Transcription Unit ◽  
Proximal Promoter ◽  
Regulatory Sequences ◽  
Cis Acting ◽  
Osteocalcin Gene ◽  
Definition Of

The human osteocalcin gene is regulated in mammalian osteoblasts by 1,25(OH)2D3-dependent and -independent mechanisms. The sequences responsible for this activity have been mapped to within the -1339 region of the gene. We show here that this enhancer region functions analogously in Saccharomyces cerevisiae cells engineered to produce active 1,25(OH)2D3 receptor. When fused to the proximal promoter elements of the yeast iso-1-cytochrome c gene, the enhancer demonstrated substantial promoter activity. This activity was elevated further by 1,25(OH)2D3 when the reporter constructs were assayed in cells containing the 1,25(OH)2D3 receptor. This system affords a model for 1,25(OH)2D3 action and represents a simple assay system that will enable definition of the important cis-acting regulatory sequences within the osteocalcin gene and identification of their cognate transcription factors.

Role for mRNA localization in translational activation but not spatial restriction of nanos RNA

Development ◽  
1999 ◽  
Vol 126 (4) ◽  
pp. 659-669 ◽  
Author(s):  
S.E. Bergsten ◽  
E.R. Gavis
Keyword(s):  
Translational Control ◽  
Rna Localization ◽  
Early Embryo ◽  
Posterior Pole ◽  
Translational Repression ◽  
Control Element ◽  
Regulatory Sequences ◽  
Cis Acting ◽  
Body Patterning ◽  
Localization Signal

Patterning of the anterior-posterior body axis during Drosophila development depends on the restriction of Nanos protein to the posterior of the early embryo. Synthesis of Nanos occurs only when maternally provided nanos RNA is localized to the posterior pole by a large, cis-acting signal in the nanos 3′ untranslated region (3′UTR); translation of unlocalized nanos RNA is repressed by a 90 nucleotide Translational Control Element (TCE), also in the 3′UTR. We now show quantitatively that the majority of nanos RNA in the embryo is not localized to the posterior pole but is distributed throughout the cytoplasm, indicating that translational repression is the primary mechanism for restricting production of Nanos protein to the posterior. Through an analysis of transgenes bearing multiple copies of nanos 3′UTR regulatory sequences, we provide evidence that localization of nanos RNA by components of the posteriorly localized germ plasm activates its translation by preventing interaction of nanos RNA with translational repressors. This mutually exclusive relationship between translational repression and RNA localization is mediated by a 180 nucleotide region of the nanos localization signal, containing the TCE. These studies suggest that the ability of RNA localization to direct wild-type body patterning also requires recognition of multiple, unique elements within the nanos localization signal by novel factors. Finally, we propose that differences in the efficiencies with which different RNAs are localized result from the use of temporally distinct localization pathways during oogenesis.

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