hnRNP G prevents inclusion on the HPV16 L1 mRNAs of the central exon between splice sites SA3358 and SD3632

Yu, Haoran; Gong, Lei; Wu, Chengjun; Nilsson, Kjell; Li-Wang, Xiaoze; Schwartz, Stefan

doi:10.1099/jgv.0.001019

Cited by 13 publications

(13 citation statements)

References 48 publications

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“…The hnRNP G has recently been shown to bind a 8-nucleotide sequence (CCGAAGAA) located downstream the SA3358 in HPV16, thus promoting the production of late mRNAs and skipping of the exon comprised between SA3358 and SD3632 in the L1 mRNA (Yu et al, 2018) (Figure 5).…”

Section: The Role Of Splicing Factors In Hpv Rnas Splicingmentioning

confidence: 99%

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Cerasuolo

Buonaguro

Tornesello

2020

Front. Cell Dev. Biol.

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The spliceosomal complex components, together with the heterogeneous nuclear ribonucleoproteins (hnRNPs) and serine/arginine-rich (SR) proteins, regulate the process of constitutive and alternative splicing, the latter leading to the production of mRNA isoforms coding multiple proteins from a single pre-mRNA molecule. The expression of splicing factors is frequently deregulated in different cancer types causing the generation of oncogenic proteins involved in cancer hallmarks. Cervical cancer is caused by persistent infection with oncogenic human papillomaviruses (HPVs) and constitutive expression of viral oncogenes. The aberrant activity of hnRNPs and SR proteins in cervical neoplasia has been shown to trigger the production of oncoproteins through the processing of pre-mRNA transcripts either derived from human genes or HPV genomes. Indeed, hnRNP and SR splicing factors have been shown to regulate the production of viral oncoprotein isoforms necessary for the completion of viral life cycle and for cell transformation. Target-therapy strategies against hnRNPs and SR proteins, causing simultaneous reduction of oncogenic factors and inhibition of HPV replication, are under development. In this review, we describe the current knowledge of the functional link between RNA splicing factors and deregulated cellular as well as viral RNA maturation in cervical cancer and the opportunity of new therapeutic strategies.

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Section: The Role Of Splicing Factors In Hpv Rnas Splicingmentioning

confidence: 99%

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Cerasuolo

Buonaguro

Tornesello

2020

Front. Cell Dev. Biol.

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“…hnRNP C also suppresses polyadenylation of cellular mRNAs [ 75 ]. It is also of interest to note that hnRNP G, which is an RNA binding protein that plays an active role in the DDR [ 58 ], also controls HPV16 L1 mRNA splicing [ 76 ]. In conclusion, DDR factors recruit hnRNP C to the HPV16 DNA, thereby promoting association of hnRNP C with de novo synthesized HPV16 mRNAs.…”

Section: Human Papillomavirus (Hpv) and The Cellular Dna Damage Rementioning

confidence: 99%

Role of the DNA Damage Response in Human Papillomavirus RNA Splicing and Polyadenylation

Nilsson

Schwartz

2018

IJMS

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Human papillomaviruses (HPVs) have evolved to use the DNA repair machinery to replicate its DNA genome in differentiated cells. HPV activates the DNA damage response (DDR) in infected cells. Cellular DDR factors are recruited to the HPV DNA genome and position the cellular DNA polymerase on the HPV DNA and progeny genomes are synthesized. Following HPV DNA replication, HPV late gene expression is activated. Recent research has shown that the DDR factors also interact with RNA binding proteins and affects RNA processing. DDR factors activated by DNA damage and that associate with HPV DNA can recruit splicing factors and RNA binding proteins to the HPV DNA and induce HPV late gene expression. This induction is the result of altered alternative polyadenylation and splicing of HPV messenger RNA (mRNA). HPV uses the DDR machinery to replicate its DNA genome and to activate HPV late gene expression at the level of RNA processing.

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“…By performing its functions in regulating transcription and pre-mRNA splicing, RBMX has been shown to perform differential activities in different viral infections. RBMX inhibits the infection of human papillomavirus type 16 by preventing the inclusion of exon on HPV16 late L1 mRNAs for splicing (27). In another setting, however, RBMX interacts with the nucleoprotein of Borna disease virus and promotes the formation of viral speckles of transcripts, leading to enhanced viral gene transcription (28).…”

mentioning

confidence: 99%

X-Linked RNA-Binding Motif Protein Modulates HIV-1 Infection of CD4 ⁺ T Cells by Maintaining the Trimethylation of Histone H3 Lysine 9 at the Downstream Region of the 5′ Long Terminal Repeat of HIV Proviral DNA

Jiang

Sun

et al. 2020

mBio

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Reversible repression of HIV-1 5′ long terminal repeat (5′-LTR)-mediated transcription represents the main mechanism for HIV-1 to maintain latency. Identification of host factors that modulate LTR activity and viral latency may help develop new antiretroviral therapies. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are known to regulate gene expression and possess multiple physiological functions. hnRNP family members have recently been identified as the sensors for viral nucleic acids to induce antiviral responses, highlighting the crucial roles of hnRNPs in regulating viral infection. A member of the hnRNP family, X-linked RNA-binding motif protein (RBMX), has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5′-LTR-driven transcription of viral genome in CD4+ T cells. Mechanistically, RBMX binds to HIV-1 proviral DNA at the LTR downstream region and maintains the repressive trimethylation of histone H3 lysine 9 (H3K9me3), leading to a blockage of the recruitment of the positive transcription factor phosphorylated RNA polymerase II (RNA pol II) and consequential impediment of transcription elongation. This RBMX-mediated modulation of HIV-1 transcription maintains viral latency by inhibiting viral reactivation from an integrated proviral DNA. Our findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies. IMPORTANCE HIV-1 latency featuring silence of transcription from HIV-1 proviral DNA represents a major obstacle for HIV-1 eradication. Reversible repression of HIV-1 5′-LTR-mediated transcription represents the main mechanism for HIV-1 to maintain latency. The 5′-LTR-driven HIV gene transcription can be modulated by multiple host factors and mechanisms. The hnRNPs are known to regulate gene expression. A member of the hnRNP family, RBMX, has been identified in this study as a novel HIV-1 restriction factor that modulates HIV-1 5′-LTR-driven transcription of viral genome in CD4+ T cells and maintains viral latency. These findings provide a new understanding of how host factors modulate HIV-1 infection and latency and suggest a potential new target for the development of HIV-1 therapies.

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hnRNP G prevents inclusion on the HPV16 L1 mRNAs of the central exon between splice sites SA3358 and SD3632

Cited by 13 publications

References 48 publications

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Role of the DNA Damage Response in Human Papillomavirus RNA Splicing and Polyadenylation

X-Linked RNA-Binding Motif Protein Modulates HIV-1 Infection of CD4 ⁺ T Cells by Maintaining the Trimethylation of Histone H3 Lysine 9 at the Downstream Region of the 5′ Long Terminal Repeat of HIV Proviral DNA

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hnRNP G prevents inclusion on the HPV16 L1 mRNAs of the central exon between splice sites SA3358 and SD3632

Cited by 13 publications

References 48 publications

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Role of the DNA Damage Response in Human Papillomavirus RNA Splicing and Polyadenylation

X-Linked RNA-Binding Motif Protein Modulates HIV-1 Infection of CD4 + T Cells by Maintaining the Trimethylation of Histone H3 Lysine 9 at the Downstream Region of the 5′ Long Terminal Repeat of HIV Proviral DNA

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X-Linked RNA-Binding Motif Protein Modulates HIV-1 Infection of CD4 ⁺ T Cells by Maintaining the Trimethylation of Histone H3 Lysine 9 at the Downstream Region of the 5′ Long Terminal Repeat of HIV Proviral DNA