Faculty Opinions recommendation of Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus.

A cDNA library was constructed from HL60 human promyelocyte poly(A)+ RNA harvested 3 h after induction of macrophage differentiation with 12-O-tetradecanoyl phorbol-13-acetate in the presence of cycloheximide. We isolated from this library a 1.6-kilobase full-length clone designated b4 whose corresponding mRNA was greatly increased in abundance in cytoplasmic RNA under these conditions. Dideoxy sequencing revealed that this mRNA encoded MONAP (monocyte-derived neutrophil-activating peptide), a 10-kilodalton monokine with neutrophil-specific chemotactic and enzyme-releasing activities. The 3' untranslated region of this mRNA was found to be 1.2 kilobases long and possessed nine copies of the AUUUA sequence known to be associated with regulation of mRNA stability. Actinomycin D chase experiments yielded evidence that cytoplasmic stabilization was one of the means of regulation of MONAP expression. Analysis of cytoplasmic poly(A)- RNA revealed the presence of several discrete truncated species that shared a common 5' end and appeared to be intermediates of degradation. S1 mapping showed that the 3' ends of these molecules were distributed throughout the 3' untranslated region, preferentially in A + U-rich regions, broadly correlating with the distribution of AUUUA sites. Nuclear run-on experiments indicated that transcriptional induction accounted for less than 15% of the accumulation of MONAP mRNA. This mRNA was induced in HL60 cells by treatment with several differentiation-inducing agents: 12-O-tetradecanoyl phorbol-13-myristate alone, sodium butyrate, vitamin D3, and dimethyl sulfoxide. It was also induced in quiescent diploid lung fibroblasts stimulated to divide by serum, and it was constitutively overexpressed by some human tumor lines.

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Exploitation of nuclear functions by human rhinovirus, a cytoplasmic RNA virus

PLoS Pathogens ◽

10.1371/journal.ppat.1007277 ◽

2018 ◽

Vol 14 (8) ◽

pp. e1007277 ◽

Cited By ~ 6

Author(s):

Dylan Flather ◽

Joseph H. C. Nguyen ◽

Bert L. Semler ◽

Paul D. Gershon

Keyword(s):

Rna Virus ◽

Human Rhinovirus ◽

Cytoplasmic Rna

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An Arenavirus RING (Zinc-Binding) Protein Binds the Oncoprotein Promyelocyte Leukemia Protein (PML) and Relocates PML Nuclear Bodies to the Cytoplasm

Journal of Virology ◽

10.1128/jvi.72.1.758-766.1998 ◽

1998 ◽

Vol 72 (1) ◽

pp. 758-766 ◽

Cited By ~ 117

Author(s):

Katherine L. B. Borden ◽

Elizabeth J. Campbell Dwyer ◽

Maria S. Salvato

Keyword(s):

Rna Virus ◽

Specific Interaction ◽

Lymphocytic Choriomeningitis ◽

Genetically Engineered ◽

Nuclear Bodies ◽

Lassa Virus ◽

Pml Nuclear Bodies ◽

Cytoplasmic Rna ◽

Localization Signal ◽

Z Protein

ABSTRACT The promyelocytic leukemia protein (PML) forms nuclear bodies which are altered in some disease conditions. We report that the cytoplasmic RNA virus lymphocytic choriomeningitis virus (LCMV) influences the distribution of PML bodies. In cells infected with LCMV, the Z protein and PML form large bodies primarily in the cytoplasm. Transient transfection studies indicate that Z alone is sufficient to redistribute PML to the cytoplasm and that PML and Z colocalize. Coimmunoprecipitation studies show specific interaction between PML and Z proteins. A similar result was observed with a Z protein from another arenavirus, Lassa virus, suggesting that this is a general feature of the Arenaviridae. Genetically engineered mutations in PML were used to show that the Z protein binds the N-terminal region of PML and does not need the PML RING or the nuclear localization signal to colocalize. The Z protein acts dominantly to overcome the diffuse phenotype observed in several PML mutants. The interaction between PML and Z may influence certain unique characteristics of arenavirus infection.

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Life cycle process dependencies of positive-sense RNA viruses suggest strategies for inhibiting productive cellular infection

Journal of The Royal Society Interface ◽

10.1098/rsif.2021.0401 ◽

2021 ◽

Vol 18 (184) ◽

Author(s):

Harsh Chhajer ◽

Vaseef A. Rizvi ◽

Rahul Roy

Keyword(s):

Life Cycle ◽

Early Life ◽

Rna Viruses ◽

Virus Assembly ◽

Rna Virus ◽

Rna Degradation ◽

Stochastic Simulations ◽

Virus Growth ◽

Cytoplasmic Rna ◽

Positive Strand Rna

Life cycle processes of positive-strand (+)RNA viruses are broadly conserved across families, yet they employ different strategies to grow in the cell. Using a generalized dynamical model for intracellular (+)RNA virus growth, we decipher these life cycle determinants and their dependencies for several viruses and parse the effects of viral mutations, drugs and host cell permissivity. We show that poliovirus employs rapid replication and virus assembly, whereas the Japanese encephalitis virus leverages its higher rate of translation and efficient cellular reorganization compared to the hepatitis C virus. Stochastic simulations demonstrate infection extinction if all seeding (inoculating) viral RNA degrade before establishing robust replication critical for infection. The probability of this productive cellular infection, ‘cellular infectivity’, is affected by virus–host processes and defined by early life cycle events and viral seeding. An increase in cytoplasmic RNA degradation and delay in vesicular compartment formation reduces infectivity, more so when combined. Synergy among these parameters in limiting (+)RNA virus infection as predicted by our model suggests new avenues for inhibiting infections by targeting the early life cycle bottlenecks.

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Regulation of the mRNA for monocyte-derived neutrophil-activating peptide in differentiating HL60 promyelocytes

Molecular and Cellular Biology ◽

10.1128/mcb.9.5.1946-1957.1989 ◽

1989 ◽

Vol 9 (5) ◽

pp. 1946-1957

Author(s):

J Kowalski ◽

D T Denhardt

Keyword(s):

Sodium Butyrate ◽

Mrna Stability ◽

Untranslated Region ◽

Actinomycin D ◽

Human Tumor ◽

Lung Fibroblasts ◽

Macrophage Differentiation ◽

Cytoplasmic Rna ◽

Transcriptional Induction ◽

Full Length Clone

A cDNA library was constructed from HL60 human promyelocyte poly(A)+ RNA harvested 3 h after induction of macrophage differentiation with 12-O-tetradecanoyl phorbol-13-acetate in the presence of cycloheximide. We isolated from this library a 1.6-kilobase full-length clone designated b4 whose corresponding mRNA was greatly increased in abundance in cytoplasmic RNA under these conditions. Dideoxy sequencing revealed that this mRNA encoded MONAP (monocyte-derived neutrophil-activating peptide), a 10-kilodalton monokine with neutrophil-specific chemotactic and enzyme-releasing activities. The 3' untranslated region of this mRNA was found to be 1.2 kilobases long and possessed nine copies of the AUUUA sequence known to be associated with regulation of mRNA stability. Actinomycin D chase experiments yielded evidence that cytoplasmic stabilization was one of the means of regulation of MONAP expression. Analysis of cytoplasmic poly(A)- RNA revealed the presence of several discrete truncated species that shared a common 5' end and appeared to be intermediates of degradation. S1 mapping showed that the 3' ends of these molecules were distributed throughout the 3' untranslated region, preferentially in A + U-rich regions, broadly correlating with the distribution of AUUUA sites. Nuclear run-on experiments indicated that transcriptional induction accounted for less than 15% of the accumulation of MONAP mRNA. This mRNA was induced in HL60 cells by treatment with several differentiation-inducing agents: 12-O-tetradecanoyl phorbol-13-myristate alone, sodium butyrate, vitamin D3, and dimethyl sulfoxide. It was also induced in quiescent diploid lung fibroblasts stimulated to divide by serum, and it was constitutively overexpressed by some human tumor lines.

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