Comprehensive annotations of human herpesvirus 6A and 6B genomes reveal novel and conserved genomic features

Yaara Finkel; Dominik Schmiedel; Julie Tai-Schmiedel; Aharon Nachshon; Roni Winkler; Martina Dobesova; Michal Schwartz; Ofer Mandelboim; Noam Stern-Ginossar

doi:10.7554/eLife.50960

Comprehensive annotations of human herpesvirus 6A and 6B genomes reveal novel and conserved genomic features

Yaara Finkel, Dominik Schmiedel, Julie Tai-Schmiedel, Aharon Nachshon, Roni Winkler, Martina Dobesova, Michal Schwartz, Ofer Mandelboim, Noam Stern-Ginossar^*

^*Corresponding author for this work

Department of Immunology and Cancer Research

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Human herpesvirus-6 (HHV-6) A and B are ubiquitous betaherpesviruses, infecting the majority of the human population. They encompass large genomes and our understanding of their protein coding potential is far from complete. Here, we employ ribosome-profiling and systematic transcript-analysis to experimentally define HHV-6 translation products. We identify hundreds of new open reading frames (ORFs), including upstream ORFs (uORFs) and internal ORFs (iORFs), generating a complete unbiased atlas of HHV-6 proteome. By integrating systematic data from the prototypic betaherpesvirus, human cytomegalovirus, we uncover numerous uORFs and iORFs conserved across betaherpesviruses and we show uORFs are enriched in late viral genes. We identified three highly abundant HHV-6 encoded long non-coding RNAs, one of which generates a non-polyadenylated stable intron appearing to be a conserved feature of betaherpesviruses. Overall, our work reveals the complexity of HHV-6 genomes and highlights novel features conserved between betaherpesviruses, providing a rich resource for future functional studies.

Original language	American English
Article number	e50960
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/eLife.50960
State	Published - Jan 2020

Bibliographical note

Funding Information:
We thank the members of the Stern-Ginossar lab for critical reading of the manuscript. This research was supported by the ICORE (Chromatin and RNA Gene Regulation, NS-G) and the Israeli Science Foundation (1526/18, NS-G). NS-G is incumbent of the Skirball career development chair in new scientists.

Funding Information:
We thank the members of the Stern-Ginossar lab for critical reading of the manuscript. This research was supported by the ICORE (Chromatin and RNA Gene Regulation, NS-G) and the Israeli Science Foundation (1526/18, NS-G). NS-G is incumbent of the Skirball career development chair in new scientists. Israeli Centers for Research Excellence. Chromatin and RNA Gene Regulation. Noam Stern-Ginossar. Israel Science Foundation. 1526/18. Noam Stern-Ginossar.

Publisher Copyright:
© Finkel et al.

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10.7554/eLife.50960

Cite this

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title = "Comprehensive annotations of human herpesvirus 6A and 6B genomes reveal novel and conserved genomic features",

abstract = "Human herpesvirus-6 (HHV-6) A and B are ubiquitous betaherpesviruses, infecting the majority of the human population. They encompass large genomes and our understanding of their protein coding potential is far from complete. Here, we employ ribosome-profiling and systematic transcript-analysis to experimentally define HHV-6 translation products. We identify hundreds of new open reading frames (ORFs), including upstream ORFs (uORFs) and internal ORFs (iORFs), generating a complete unbiased atlas of HHV-6 proteome. By integrating systematic data from the prototypic betaherpesvirus, human cytomegalovirus, we uncover numerous uORFs and iORFs conserved across betaherpesviruses and we show uORFs are enriched in late viral genes. We identified three highly abundant HHV-6 encoded long non-coding RNAs, one of which generates a non-polyadenylated stable intron appearing to be a conserved feature of betaherpesviruses. Overall, our work reveals the complexity of HHV-6 genomes and highlights novel features conserved between betaherpesviruses, providing a rich resource for future functional studies.",

author = "Yaara Finkel and Dominik Schmiedel and Julie Tai-Schmiedel and Aharon Nachshon and Roni Winkler and Martina Dobesova and Michal Schwartz and Ofer Mandelboim and Noam Stern-Ginossar",

note = "Funding Information: We thank the members of the Stern-Ginossar lab for critical reading of the manuscript. This research was supported by the ICORE (Chromatin and RNA Gene Regulation, NS-G) and the Israeli Science Foundation (1526/18, NS-G). NS-G is incumbent of the Skirball career development chair in new scientists. Funding Information: We thank the members of the Stern-Ginossar lab for critical reading of the manuscript. This research was supported by the ICORE (Chromatin and RNA Gene Regulation, NS-G) and the Israeli Science Foundation (1526/18, NS-G). NS-G is incumbent of the Skirball career development chair in new scientists. Israeli Centers for Research Excellence. Chromatin and RNA Gene Regulation. Noam Stern-Ginossar. Israel Science Foundation. 1526/18. Noam Stern-Ginossar. Publisher Copyright: {\textcopyright} Finkel et al.",

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AU - Mandelboim, Ofer

AU - Stern-Ginossar, Noam

N1 - Funding Information: We thank the members of the Stern-Ginossar lab for critical reading of the manuscript. This research was supported by the ICORE (Chromatin and RNA Gene Regulation, NS-G) and the Israeli Science Foundation (1526/18, NS-G). NS-G is incumbent of the Skirball career development chair in new scientists. Funding Information: We thank the members of the Stern-Ginossar lab for critical reading of the manuscript. This research was supported by the ICORE (Chromatin and RNA Gene Regulation, NS-G) and the Israeli Science Foundation (1526/18, NS-G). NS-G is incumbent of the Skirball career development chair in new scientists. Israeli Centers for Research Excellence. Chromatin and RNA Gene Regulation. Noam Stern-Ginossar. Israel Science Foundation. 1526/18. Noam Stern-Ginossar. Publisher Copyright: © Finkel et al.

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N2 - Human herpesvirus-6 (HHV-6) A and B are ubiquitous betaherpesviruses, infecting the majority of the human population. They encompass large genomes and our understanding of their protein coding potential is far from complete. Here, we employ ribosome-profiling and systematic transcript-analysis to experimentally define HHV-6 translation products. We identify hundreds of new open reading frames (ORFs), including upstream ORFs (uORFs) and internal ORFs (iORFs), generating a complete unbiased atlas of HHV-6 proteome. By integrating systematic data from the prototypic betaherpesvirus, human cytomegalovirus, we uncover numerous uORFs and iORFs conserved across betaherpesviruses and we show uORFs are enriched in late viral genes. We identified three highly abundant HHV-6 encoded long non-coding RNAs, one of which generates a non-polyadenylated stable intron appearing to be a conserved feature of betaherpesviruses. Overall, our work reveals the complexity of HHV-6 genomes and highlights novel features conserved between betaherpesviruses, providing a rich resource for future functional studies.

AB - Human herpesvirus-6 (HHV-6) A and B are ubiquitous betaherpesviruses, infecting the majority of the human population. They encompass large genomes and our understanding of their protein coding potential is far from complete. Here, we employ ribosome-profiling and systematic transcript-analysis to experimentally define HHV-6 translation products. We identify hundreds of new open reading frames (ORFs), including upstream ORFs (uORFs) and internal ORFs (iORFs), generating a complete unbiased atlas of HHV-6 proteome. By integrating systematic data from the prototypic betaherpesvirus, human cytomegalovirus, we uncover numerous uORFs and iORFs conserved across betaherpesviruses and we show uORFs are enriched in late viral genes. We identified three highly abundant HHV-6 encoded long non-coding RNAs, one of which generates a non-polyadenylated stable intron appearing to be a conserved feature of betaherpesviruses. Overall, our work reveals the complexity of HHV-6 genomes and highlights novel features conserved between betaherpesviruses, providing a rich resource for future functional studies.

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Comprehensive annotations of human herpesvirus 6A and 6B genomes reveal novel and conserved genomic features

Abstract

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