Transcripts Encoding K12, v-FLIP, v-Cyclin, and the MicroRNA Cluster of Kaposi's Sarcoma-Associated Herpesvirus Originate from a Common Promoter

Pearce, Michael J.; Matsumura, Satoko; Wilson, Angus C.

doi:10.1128/jvi.79.22.14457-14464.2005

Cited by 100 publications

(104 citation statements)

References 54 publications

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“…Many of the genes expressed during latent infection Xank the genomic region encoding the viral miRNAs. Detailed mapping of the latent transcripts in two independent studies have subsequently identiWed three overlapping transcripts driven by two separate promoters that have the potential to encode 10 of the 11 miRNAs within a single intron [39,40]. All ten miRNAs were detected following the transient transfection of the genomic region encoding the transcripts, strongly suggesting that all ten miRNAs are in fact encoded for within the identiWed intron [40].…”

Section: Kaposi's Sarcoma-associated Herpesvirusmentioning

confidence: 99%

The functions of herpesvirus-encoded microRNAs

Grey

Hook

Nelson

2007

Med Microbiol Immunol

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Bioinformatic and direct cloning approaches have led to the identiWcation of over 100 novel miRNAs expressed in DNA viruses, although the function of the majority of these small regulatory RNA molecules is unclear. Recently, a number of reports have now identiWed potential targets of viral miRNAs, including cellular and viral genes as well as an ortholog of an important immunoregulatory cellular miRNA. In this review, we will cover the identiWcation and characterization of miRNAs expressed in the herpesvirus family and discuss the potential signiWcance of their role in viral infection.

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Section: Kaposi's Sarcoma-associated Herpesvirusmentioning

confidence: 99%

The functions of herpesvirus-encoded microRNAs

Grey

Hook

Nelson

2007

Med Microbiol Immunol

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“…It has been shown that expression of LANA can be directed from two different promoters that generate different 5′ UTRs of LANA mRNA. Although the constitutive (latent) promoter generates a longer 5′ UTR that occurs in a spliced or unspliced form, the lytic LANA promoter, localized in the intron within the LANA 5′ UTR, directs the expression of an unspliced mRNA with a shorter 5′ UTR (4,57,58). One could envisage that the shorter 5′ UTR generated during lytic reactivation could favor, as a result of a different RNA structure fold, the use of internal start codons in the LANA NTD and thereby the generation of LANA variants lacking the N-terminal NLS (4,5), which localize to the cytoplasm.…”

Section: ) (B and C)mentioning

confidence: 99%

Cytoplasmic isoforms of Kaposi sarcoma herpesvirus LANA recruit and antagonize the innate immune DNA sensor cGAS

Zhang

Chan

Samarina

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

136

140

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The latency-associated nuclear antigen (LANA) of Kaposi sarcoma herpesvirus (KSHV) is mainly localized and functions in the nucleus of latently infected cells, playing a pivotal role in the replication and maintenance of latent viral episomal DNA. In addition, N-terminally truncated cytoplasmic isoforms of LANA, resulting from internal translation initiation, have been reported, but their function is unknown. Using coimmunoprecipitation and MS, we found the cGMP-AMP synthase (cGAS), an innate immune DNA sensor, to be a cellular interaction partner of cytoplasmic LANA isoforms. By directly binding to cGAS, LANA, and particularly, a cytoplasmic isoform, inhibit the cGAS-STING-dependent phosphorylation of TBK1 and IRF3 and thereby antagonize the cGASmediated restriction of KSHV lytic replication. We hypothesize that cytoplasmic forms of LANA, whose expression increases during lytic replication, inhibit cGAS to promote the reactivation of the KSHV from latency. This observation points to a novel function of the cytoplasmic isoforms of LANA during lytic replication and extends the function of LANA from its role during latency to the lytic replication cycle.KSHV | cytoplasmic LANA | cyclic GMP-AMP synthase

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“…Sequences between LIR19 and ORF71, furthermore, can serve as an origin of replication during the lytic lifecycle of KSHV ( Line ta l. 2003;AuCoin et al 2004;W ang et al 2004). Recently, at ranscriptt hat is likely to represent a pri-miRNA for the various pre-miRNAs has been identified (Li et al 2002;Pearce et al 2005; see Fig.6 ,2 .5-kb LTdtranscript). The transcript is coterminal with ap reviously described mRNA transcript for Kaposin (Sadler et al 1999); however, it starts several kilobases further upstream and encompassesall of the pre-miRNAs (as well as ORFs 71 and 72).…”

Section: Confirmation Of Kshv Pre-mirnas By Microarray Analysis and Nmentioning

confidence: 99%

A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses

Grundhoff¹,

Sullivan²,

Ganem³

2006

RNA

409

364

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We have developed an approach to identify microRNAs (miRNAs) that is based on bioinformatics and array-based technologies, without the use of cDNA cloning. The approach, designed for use on genomes of small size ( < 2Mb), was tested on cells infected by either of two lymphotropic herpesviruses, KSHV and EBV. The viral genomes were scanned computationally for pre-miRNAs using an algorithm (VMir) we have developed. Candidate hairpins suggested by this analysis were then synthesized as oligonucleotides on microarrays, and the arrays were hybridized with small RNAs from infected cells. Candidate miRNAs that scored positive on the arrays were then subjected to confirmatory Northern blot analysis. Using this approach, 10 of the known KSHV pre-miRNAs were identified, as well as anovel pre-miRNA that had earlier escaped detection. This method also led to the identification of seven new EBV-encoded pre-miRNAs; by using additional computational approaches, we identified atotal of 18 new EBV pre-miRNAs that produce 22 mature miRNA molecules, thereby more than quadrupling the total number of hitherto known EBV miRNAs. The advantages and limitations of the approach are discussed.

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Transcripts Encoding K12, v-FLIP, v-Cyclin, and the MicroRNA Cluster of Kaposi's Sarcoma-Associated Herpesvirus Originate from a Common Promoter

Cited by 100 publications

References 54 publications

The functions of herpesvirus-encoded microRNAs

The functions of herpesvirus-encoded microRNAs

Cytoplasmic isoforms of Kaposi sarcoma herpesvirus LANA recruit and antagonize the innate immune DNA sensor cGAS

A combined computational and microarray-based approach identifies novel microRNAs encoded by human gamma-herpesviruses

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