scholarly journals Host Noncoding Retrotransposons Induced by DNA Viruses: a SINE of Infection?

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
Jessica M. Tucker ◽  
Britt A. Glaunsinger
Keyword(s):  
Gene Expression ◽  
Life Cycle ◽  
Virus Infection ◽  
Rna Polymerase ◽  
Reverse Transcription ◽  
Noncoding Rna ◽  
Rna Polymerase Iii ◽  
Dna Virus ◽  
Dna Viruses ◽  
Gene Regulatory

ABSTRACT Our genomes are dominated by repetitive elements. The majority of these elements derive from retrotransposons, which expand throughout the genome through a process of reverse transcription and integration. Short interspersed nuclear elements, or SINEs, are an abundant class of retrotransposons that are transcribed by RNA polymerase III, thus generating exclusively noncoding RNA (ncRNA) that must hijack the machinery required for their transposition. SINE loci are generally transcriptionally repressed in somatic cells but can be robustly induced upon infection with multiple DNA viruses. Recent research has focused on the gene expression and signaling events that are modulated by SINE ncRNAs, particularly during gammaherpesvirus infection. Here, we review the biology of these SINE ncRNAs, explore how DNA virus infection may lead to their induction, and describe how novel gene regulatory and immune-related functions of these ncRNAs may impact the viral life cycle.

scholarly journals Alteration of the premature tRNA landscape by gammaherpesvirus infection

2019 ◽  
Author(s):  
Jessica Tucker ◽  
Aaron M. Schaller ◽  
Ian Willis ◽  
Britt A. Glaunsinger
Keyword(s):  
Virus Infection ◽  
Rna Polymerase ◽  
Viral Infection ◽  
Rna Polymerase Iii ◽  
Trna Genes ◽  
Dna Virus ◽  
Transfer Rnas ◽  
Genome Wide Analysis ◽  
Polymerase Iii ◽  
Genome Wide

AbstractTransfer RNAs (tRNAs) are transcribed by RNA polymerase III (RNAPIII) and play a central role in decoding our genome, yet their expression and non-canonical function remain understudied. Many DNA tumor viruses enhance the activity of RNAPIII, yet whether infection alters tRNA expression is largely unknown. Here, we present the first genome-wide analysis of how viral infection alters the tRNAome. Using a tRNA-specific sequencing method (DM-tRNA-seq), we find that the murine gammaherpesvirus MHV68 induces global changes in pre-tRNA expression with 14% of tRNA genes upregulated more than 3-fold, indicating that differential tRNA gene induction is a characteristic of DNA virus infection. Elevated pre-tRNA expression corresponds to increased RNAPIII occupancy for the subset of tRNA genes tested; additionally, post-transcriptional mechanisms contribute to the accumulation of pre-tRNA species. We find increased abundance of tRNA fragments derived from pre-tRNAs upregulated by viral infection, suggesting that non-canonical tRNA cleavage is also affected. Further, pre-tRNA accumulation, but not RNAPIII recruitment, requires gammaherpesvirus-induced degradation of host mRNAs by the virally encoded mRNA endonuclease muSOX. We hypothesize that depletion of pre-tRNA maturation or turnover machinery contributes to robust accumulation of full-length pre-tRNAs in infected cells. Collectively, these findings reveal pervasive changes to tRNA expression during DNA virus infection and highlight the potential of using viruses to explore tRNA biology.SignificanceViral infection can dramatically change the gene expression landscape of the host cell, yet little is known regarding changes in non-coding gene transcription by RNA polymerase III (RNAPIII). Among these are transfer RNAs (tRNAs), which are fundamental in protein translation, yet whose gene regulatory features remain largely undefined in mammalian cells. Here, we perform the first genome-wide analysis of tRNA expression changes during viral infection. We show that premature tRNAs accumulate during infection with the model gammaherpesvirus MHV68 as a consequence of increased transcription, but that transcripts do not undergo canonical maturation into mature tRNAs. These findings underscore how tRNA expression is a highly-regulated process and that cells have strategies to balance tRNA pools during conditions of elevated RNAPIII activity.

scholarly journals Alteration of the Premature tRNA Landscape by Gammaherpesvirus Infection

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. e02664-20
Author(s):  
Jessica M. Tucker ◽  
Aaron M. Schaller ◽  
Ian Willis ◽  
Britt A. Glaunsinger
Keyword(s):  
Virus Infection ◽  
Rna Polymerase ◽  
Viral Infection ◽  
Rna Polymerase Iii ◽  
Trna Genes ◽  
Dna Virus ◽  
Transfer Rnas ◽  
Genome Wide Analysis ◽  
Polymerase Iii ◽  
Genome Wide

ABSTRACTTransfer RNAs (tRNAs) are transcribed by RNA polymerase III (RNAPIII) and play a central role in decoding our genome, yet their expression and noncanonical function remain understudied. Many DNA tumor viruses enhance the activity of RNAPIII, yet whether infection alters tRNA expression is largely unknown. Here, we present the first genome-wide analysis of how viral infection alters the tRNAome. Using a tRNA-specific sequencing method (DM-tRNA-seq), we find that the murine gammaherpesvirus MHV68 induces global changes in premature tRNA (pre-tRNA) expression, with 14% of tRNA genes upregulated more than 3-fold, indicating that differential tRNA gene induction is a characteristic of DNA virus infection. Elevated pre-tRNA expression corresponds to increased RNAPIII occupancy for the subset of tRNA genes tested; additionally, posttranscriptional mechanisms contribute to the accumulation of pre-tRNA species. We find increased abundance of tRNA fragments derived from pre-tRNAs upregulated by viral infection, suggesting that noncanonical tRNA cleavage is also affected. Furthermore, pre-tRNA accumulation, but not RNAPIII recruitment, requires gammaherpesvirus-induced degradation of host mRNAs by the virally encoded mRNA endonuclease muSOX. We hypothesize that depletion of pre-tRNA maturation or turnover machinery contributes to robust accumulation of full-length pre-tRNAs in infected cells. Collectively, these findings reveal pervasive changes to tRNA expression during DNA virus infection and highlight the potential of using viruses to explore tRNA biology.IMPORTANCE Viral infection can dramatically change the gene expression landscape of the host cell, yet little is known regarding changes in noncoding gene transcription by RNA polymerase III (RNAPIII). Among these are transfer RNAs (tRNAs), which are fundamental in protein translation, yet whose gene regulatory features remain largely undefined in mammalian cells. Here, we perform the first genome-wide analysis of tRNA expression changes during viral infection. We show that premature tRNAs accumulate during infection with the model gammaherpesvirus MHV68 as a consequence of increased transcription, but that transcripts do not undergo canonical maturation into mature tRNAs. These findings underscore how tRNA expression is a highly regulated process, especially during conditions of elevated RNAPIII activity.

scholarly journals What functional genomics has taught us about transcriptional regulation in malaria parasites

2019 ◽  
Vol 18 (5) ◽  
pp. 290-301 ◽  
Author(s):  
Christa G Toenhake ◽  
Richárd Bártfai
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Life Cycle ◽  
Functional Genomics ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Complex Life Cycle ◽  
Malaria Parasites ◽  
Gene Regulatory

Abstract Malaria parasites are characterized by a complex life cycle that is accompanied by dynamic gene expression patterns. The factors and mechanisms that regulate gene expression in these parasites have been searched for even before the advent of next generation sequencing technologies. Functional genomics approaches have substantially boosted this area of research and have yielded significant insights into the interplay between epigenetic, transcriptional and post-transcriptional mechanisms. Recently, considerable progress has been made in identifying sequence-specific transcription factors and DNA-encoded regulatory elements. Here, we review the insights obtained from these efforts including the characterization of core promoters, the involvement of sequence-specific transcription factors in life cycle progression and the mapping of gene regulatory elements. Furthermore, we discuss recent developments in the field of functional genomics and how they might contribute to further characterization of this complex gene regulatory network.

scholarly journals Human IFIT3 Protein Induces Interferon Signaling and Inhibits Adenovirus Immediate Early Gene Expression

mBio ◽  
2021 ◽  
Author(s):  
Aniska Chikhalya ◽  
Meike Dittmann ◽  
Yueting Zheng ◽  
Sook-Young Sohn ◽  
Charles M. Rice ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Viruses ◽  
Early Gene ◽  
Immediate Early ◽  
Interferon Signaling ◽  
Dna Virus ◽  
Dna Viruses ◽  
Early Gene Expression ◽  
Partner Proteins ◽  
Induced Proteins

IFITs belong to a family of IFN-induced proteins that have broad antiviral functions, primarily studied with RNA viruses leaving a gap of knowledge on the effects of these proteins on DNA viruses. In this study we show that IFIT3, with its partner proteins IFIT1 and IFIT2, specifically restricts replication of human Ad, a DNA virus, by stimulating IFNβ production via the STING and MAVS pathways.

scholarly journals PCV2 targets cGAS to inhibit type I interferon induction to promote other DNA virus infection

2021 ◽  
Vol 17 (9) ◽  
pp. e1009940
Author(s):  
Zhenyu Wang ◽  
Jing Chen ◽  
Xingchen Wu ◽  
Dan Ma ◽  
Xiaohua Zhang ◽  
...  
Keyword(s):  
Virus Infection ◽  
Type I Interferon ◽  
Akt Signaling ◽  
Pcv2 Infection ◽  
Regulation Mechanism ◽  
Type I ◽  
Histone Deacetylase 6 ◽  
Dna Virus ◽  
Dna Viruses ◽  
Interferon Induction

Viruses use diverse strategies to impair the antiviral immunity of host in order to promote infection and pathogenesis. Herein, we found that PCV2 infection promotes the infection of DNA viruses through inhibiting IFN-β induction in vivo and in vitro. In the early phase of infection, PCV2 promotes the phosphorylation of cGAS at S278 via activation of PI3K/Akt signaling, which directly silences the catalytic activity of cGAS. Subsequently, phosphorylation of cGAS at S278 can facilitate the K48-linked poly-ubiquitination of cGAS at K389, which can been served as a signal for recognizing by the ubiquitin-binding domain of histone deacetylase 6 (HDAC6), to promote the translocation of K48-ubiquitinated-cGAS from cytosol to autolysosome depending on the deacetylase activity of HDAC6, thereby eventually resulting in a markedly increased cGAS degradation in PCV2 infection-induced autophagic cells relative to Earle’s Balanced Salt Solution (EBSS)-induced autophagic cells (a typical starving autophagy). Importantly, we found that PCV2 Cap and its binding protein gC1qR act as predominant regulators to promote porcine cGAS phosphorylation and HDAC6 activation through mediating PI3K/AKT signaling and PKCδ signaling activation. Based on this finding, gC1qR-binding activity deficient PCV2 mutant (PCV2RmA) indeed show a weakened inhibitory effect on IFN-β induction and a weaker boost effect for other DNA viruses infection compared to wild-type PCV2. Collectively, our findings illuminate a systematic regulation mechanism by which porcine circovirus counteracts the cGAS-STING signaling pathway to inhibit the type I interferon induction and promote DNA virus infection, and identify gC1qR as an important regulator for the immunosuppression induced by PCV2.

scholarly journals Mitotic regulation of a TATA-binding-protein-containing complex.

1995 ◽  
Vol 15 (4) ◽  
pp. 1983-1992 ◽  
Author(s):  
R J White ◽  
T M Gottlieb ◽  
C S Downes ◽  
S P Jackson
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Hela Cells ◽  
Transcriptional Repression ◽  
Molecular Basis ◽  
Binding Protein ◽  
Rna Polymerase Iii ◽  
Tata Binding Protein ◽  
Polymerase Iii ◽  
Mitotic Regulation

The mitotic state is associated with a generalized repression of transcription. We show that mitotic repression of RNA polymerase III transcription can be reproduced by using extracts of synchronized HeLa cells. We have used this system to investigate the molecular basis of transcriptional repression during mitosis. We find a specific decrease in the activity of the TATA-binding-protein (TBP)-containing complex TFIIIB. TBP itself is hyperphosphorylated at mitosis, but this does not appear to account for the loss of TFIIIB activity. Instead, one or more TBP-associated components appear to be regulated. The data suggest that changes in the activity of TBP-associated components contribute to the coordinate repression of gene expression that occurs at mitosis.

Sign in / Sign up

Export Citation Format

Share Document