Department of Medical Biology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
MTA -SZTE Lendület GeMiNI Research Group, University of Szeged, Szeged, Hungary.
Sci Rep. 2023 Sep 29;13(1):16395. doi: 10.1038/s41598-023-43344-y.
Long-read sequencing (LRS) techniques enable the identification of full-length RNA molecules in a single run eliminating the need for additional assembly steps. LRS research has exposed unanticipated transcriptomic complexity in various organisms, including viruses. Herpesviruses are known to produce a range of transcripts, either close to or overlapping replication origins (Oris) and neighboring genes related to transcription or replication, which possess confirmed or potential regulatory roles. In our research, we employed both new and previously published LRS and short-read sequencing datasets to uncover additional Ori-proximal transcripts in nine herpesviruses from all three subfamilies (alpha, beta and gamma). We discovered novel long non-coding RNAs, as well as splice and length isoforms of mRNAs. Moreover, our analysis uncovered an intricate network of transcriptional overlaps within the examined genomic regions. We demonstrated that herpesviruses display distinct patterns of transcriptional overlaps in the vicinity of or at the Oris. Our findings suggest the existence of a 'super regulatory center' in the genome of alphaherpesviruses that governs the initiation of both DNA replication and global transcription through multilayered interactions among the molecular machineries.
长读测序 (LRS) 技术可在单次运行中识别全长 RNA 分子，无需额外的组装步骤。LRS 研究揭示了各种生物体（包括病毒）中意想不到的转录组复杂性。已知疱疹病毒会产生一系列转录本，这些转录本要么靠近或重叠复制起点 (Ori) 和与转录或复制相关的邻近基因，它们具有已确认或潜在的调节作用。在我们的研究中，我们同时使用了新的和以前发表的 LRS 和短读测序数据集，以在来自三个亚科（α、β和γ）的九种疱疹病毒中发现更多 Ori 近端转录本。我们发现了新的长非编码 RNA 以及 splice 和 mRNA 长度异构体。此外，我们的分析揭示了所研究基因组区域内转录重叠的复杂网络。我们表明，疱疹病毒在 Ori 附近或 Ori 处显示出不同的转录重叠模式。我们的研究结果表明，α疱疹病毒基因组中存在一个“超级调控中心”，通过分子机制之间的多层次相互作用，对 DNA 复制和全局转录的启动进行调控。
