Identification of protein partners of the human immunodeficiency virus 1<i>tat</i>/<i>rev</i>exon 3 leads to the discovery of a new HIV-1 splicing regulator, protein hnRNP K

Marchand, Virginie; Santerre, Maryline; Aigueperse, Christelle; Fouillen, Laëtitia; Saliou, Jean‐Michel; Dorsselaer, Alain Van; Sanglier-Cianférani, Sarah; Branlant, Christiane; Motorin, Yuri

doi:10.4161/rna.8.2.13984

Cited by 41 publications

(49 citation statements)

References 72 publications

(141 reference statements)

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“…Furthermore, hnRNP Q is capable of influencing IRES-dependent mRNA translation [16-18]. In the HIV system, hnRNP Q was recently shown to be part of a group of cellular proteins that binds to a segment of HIV-1 RNA containing splice acceptor site A7 [19] located near the RRE. Interestingly, the group of proteins binding to this region also included translational factors.…”

Section: Resultsmentioning

confidence: 99%

Heterogenous nuclear ribonucleoprotein Q increases protein expression from HIV-1 Rev-dependent transcripts

Vincendeau

Nagel

Brenke

et al. 2013

Virol J

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BackgroundHeterogenous nuclear ribonucleoproteins (hnRNPs) control many processes of the gene expression machinery including mRNA transcription, splicing, export, stability and translation. Recent data show interaction of the HIV-1 Rev regulatory protein with a subset of hnRNP proteins, that includes hnRNP Q, suggesting that hnRNPs can contribute to regulation of HIV-1 gene expression by Rev.FindingsIn this work we address the effect of hnRNP Q on Rev-dependent gene expression. We show that hnRNP Q overexpression increased levels of proteins produced from a Rev-dependent reporter gene in the presence of Rev. Increased protein levels did not correlate with changes in either the levels or the nucleocytoplasmic distribution of Rev-dependent reporter mRNAs. Similar observations were made in persistently HIV-1 infected HeLa cells. In these cells, hnRNP Q overexpression increased levels of the HIV-1 Gag-p24 protein, while levels of viral Rev-dependent mRNAs were not affected.ConclusionOur data indicate that hnRNP Q can stimulate the protein production of Rev-dependent mRNAs without changing mRNA levels and mRNA export, respectively. This suggests that hnRNP Q can boost HIV gene expression at the level of protein production.

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Section: Resultsmentioning

confidence: 99%

Heterogenous nuclear ribonucleoprotein Q increases protein expression from HIV-1 Rev-dependent transcripts

Vincendeau

Nagel

Brenke

et al. 2013

Virol J

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“…The second HIV-1 derived transcript (SLS123 RNA) contained the SLS2 region along with two additional stem-loop structures at 5′- and 3′-extremities (nt 7903–8092 in HIV-1 RNA). Both fragments had previously been shown to bind hnRNP A1 protein with high affinity and the binding sites for hnRNP A1 had been determined by footprinting studies (39,49). …”

Section: Resultsmentioning

confidence: 99%

“…RNA binary and ternary oligonucleotides were from Biomers, Ulm, Germany [G/U (3′-GGUUGUGGUGGUUUGUUGGU), G/C (3′-CCGGCCCGGCGGCCGGCGCG), U/C (3′-UUCUUUCUUUCCCUUCCUUU), U/A (3′-UUAUAUUUAUAAAUAUUAAA)], Iba, Göttingen, Germany [CUG: (3′-CUUCGUUCGCUGGUC, GAC: (3′-GACCAGCGAACGAAGCAGG)] and Sigma-Aldrich [G/A (3′-AAAGGAAGGGAAAGAAAGAA), C/A (3′-ACCAACAAACCACCACAACC), G/C (3′-CCGGCCCGGCGGCCGGCGCG)]. In vitro transcription was conducted as previously described for S. cerevisiae tRNA Phe (21), and MS2 and HIV-derived RNAs (39), respectively.…”

Section: Methodsmentioning

confidence: 99%

A multifunctional bioconjugate module for versatile photoaffinity labeling and click chemistry of RNA

Kellner

Seidu-Larry

Burhenne

et al. 2011

Nucleic Acids Research

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A multifunctional reagent based on a coumarin scaffold was developed for derivatization of naive RNA. The alkylating agent N3BC [7-azido-4-(bromomethyl)coumarin], obtained by Pechmann condensation, is selective for uridine. N3BC and its RNA conjugates are pre-fluorophores which permits controlled modular and stepwise RNA derivatization. The success of RNA alkylation by N3BC can be monitored by photolysis of the azido moiety, which generates a coumarin fluorophore that can be excited with UV light of 320 nm. The azidocoumarin-modified RNA can be flexibly employed in structure-function studies. Versatile applications include direct use in photo-crosslinking studies to cognate proteins, as demonstrated with tRNA and RNA fragments from the MS2 phage and the HIV genome. Alternatively, the azide function can be used for further derivatization by click-chemistry. This allows e.g. the introduction of an additional fluorophore for excitation with visible light.

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“…Its interactions with viral components and/or cellular factors support the replication of viruses, including enterovirus 71, Sindbis virus, dengue virus, chikungunya virus, hepatitis C virus, HBV, HIV-1, HSV-1, African swine fever virus, human cytomegalovirus, and Epstein-Barr virus (16,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Interestingly, in human cytomegalovirus-infected cells, hnRNP K is essential for virus replication as it promotes the viability of infected cells (28).…”

Section: Discussionmentioning

confidence: 99%

“…Dengue virus and herpes simplex virus 1 (HSV-1) also have been shown to require the functions of hnRNP K in progeny virus production (20,21). hnRNP K not only serves as a splicing factor for Tat/Rev exon 3 of HIV-1 (22) but also interacts with viral components of Sindbis virus, chikungunya virus, hepatitis C virus, African swine fever virus, human cytomegalovirus (CMV), and Epstein-Barr virus (23)(24)(25)(26)(27)(28) to support virus growth.…”

mentioning

confidence: 99%

Heterogeneous Nuclear Ribonucleoprotein K Supports Vesicular Stomatitis Virus Replication by Regulating Cell Survival and Cellular Gene Expression

Dinh

Das

Franco

et al. 2013

J Virol

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The heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a member of the family of hnRNPs and was recently shown in a genome-wide small interfering RNA (siRNA) screen to support vesicular stomatitis virus (VSV) growth. To decipher the role of hnRNP K in VSV infection, we conducted studies which suggest that the protein is required for VSV spreading. Virus binding to cells, entry, and nucleocapsid uncoating steps were not adversely affected in the absence of hnRNP K, whereas viral genome transcription and replication were reduced slightly. These results indicate that hnRNP K is likely involved in virus assembly and/or release from infected cells. Further studies showed that hnRNP K suppresses apoptosis of virus-infected cells, resulting in increased cell survival during VSV infection. The increased survival of the infected cells was found to be due to the suppression of proapoptotic proteins such as Bcl-X S and Bik in a cell-type-dependent manner. Additionally, depletion of hnRNP K resulted in not only significantly increased levels of T-cell-restricted intracellular antigen 1 (TIA1) but also switching of the expression of the two isoforms of the protein (TIA1a and TIA1b), both of which inhibited VSV replication. hnRNP K was also found to support expression of several cellular proteins known to be required for VSV infection. Overall, our studies demonstrate hnRNP K to be a multifunctional protein that supports VSV infection via its role(s) in suppressing apoptosis of infected cells, inhibiting the expression of antiviral proteins, and maintaining the expression of proteins required for the virus.

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Identification of protein partners of the human immunodeficiency virus 1tat/revexon 3 leads to the discovery of a new HIV-1 splicing regulator, protein hnRNP K

Cited by 41 publications

References 72 publications

Heterogenous nuclear ribonucleoprotein Q increases protein expression from HIV-1 Rev-dependent transcripts

Heterogenous nuclear ribonucleoprotein Q increases protein expression from HIV-1 Rev-dependent transcripts

A multifunctional bioconjugate module for versatile photoaffinity labeling and click chemistry of RNA

Heterogeneous Nuclear Ribonucleoprotein K Supports Vesicular Stomatitis Virus Replication by Regulating Cell Survival and Cellular Gene Expression

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