ABSTRACT
In the last couple of years, the rapid advances and decreasing costs of sequencing technologies have revolutionized transcriptomic research. Long-read sequencing (LRS) techniques are able to detect full-length RNA molecules in a single run without the need for additional assembly steps. LRS studies have revealed an unexpected transcriptomic complexity in a variety of organisms, including viruses. A number of transcripts with proven or putative regulatory role, mapping close to or overlapping the replication origins (Oris) and the nearby transcription activator genes, have been described in herpesviruses. In this study, we applied both newly generated and previously published LRS and short-read sequencing datasets to discover additional Ori-proximal transcripts in nine herpesviruses belonging to all of the three subfamilies (alpha, beta and gamma). We identified novel long non-coding RNAs (lncRNAs), as well as splice and length isoforms of mRNAs and lncRNAs. Furthermore, our analysis disclosed an intricate meshwork of transcriptional overlaps at the examined genomic regions. Our results suggest the existence of a ‘super regulatory center’, which controls both the replication and the global transcription through multilevel interactions between the molecular machineries.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- αHV
- alphaherpesvirus
- asRNA
- antisense RNA
- βHV
- betaherpesvirus
- BoHV-1
- Bovine alphaherpesvirus 1
- CDS
- coding sequence
- DBP
- DNA-binding protein
- DNP
- DNA polymerase
- dRNA-Seq
- direct RNA sequencing
- dcDNA-Seq
- direct cDNA sequencing
- E
- early
- EBV
- Epstein-Barr virus
- EHV-1
- Equid alphaherpesvirus
- γHV
- gammaherpesvirus
- HCMV
- Human cytomegalovirus
- HHV-6
- Human herpesvirus 6
- HSV-1
- Herpes simplex virus 1
- IE
- immediate-early
- ICP
- infected cell polypeptide
- IR
- inverted repeat
- IRL
- internal repeat of UL region
- IRS
- internal repeat of US region
- L
- late
- LAT
- latency-associated transcript
- LLT
- long latency transcript
- lncRNA
- long noncoding
- RNA LRS
- long-read sequencing
- L/ST
- L/S junction-spanning transcript
- miRNA
- micro RNA
- ncRNA
- non-coding RNA
- ONT
- Oxford Nanopore Technologies
- ORC
- origin recognition complex
- ORF
- open reading frame
- Ori
- replication origin
- PacBio
- Pacific Biosciences
- PRV
- Pseudorabies virus
- raRNA
- replication origin-associated
- RNA RNP
- RNA polymerase
- SRS
- short-read sequencing
- SVV
- Simian varicella virus
- TES
- transcript end site
- TF
- transcription factor
- TI
- transcript isoform
- TO
- transcriptional overlap
- TR
- transcription regulator
- TRL
- terminal repeat of UL region
- TRS
- terminal repeat of US region
- TSS
- transcript start site
- UL
- unique long
- ES
- unique short
- UTR
- untranslated region
- VZV
- Varicella-zoster virus