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 |
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Article number | e50960 |
Journal | eLife |
Volume | 9 |
DOIs | |
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.