Dataset Information

Functional and molecular dissection of viral lncRNAs throughout HCMV life cycle

ABSTRACT: Small, compact genomes confer a selective advantage to viruses, yet human cytomegalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs) RNA1.2, RNA2.7, RNA4.9, and RNA5.0. These lncRNAs account for majority of the viral transcriptome, but their functions remain largely unknown. Here, we showed that HCMV lncRNAs, except for RNA5.0, are required throughout the entire viral life cycle. Deletion of each lncRNA resulted in a decrease in viral progeny during lytic replication and failing to efficiently establish latent reservoirs and reactivate. Nanopore direct RNA sequencing of native lncRNA molecules revealed that each lncRNA exhibited a dynamic modification landscape, depending on the state of infection. Global analysis of the lncRNA interactome identified 32, 11, and 89 host factors that specifically bind to RNA1.2, RNA2.7, and RNA4.9, respectively. Moreover, 52 proteins commonly bound to the three lncRNAs were identified, including 11 antiviral immunity-related proteins. Our molecular analyses found that three lncRNAs are modified with N⁶-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth functional analysis revealed that m6A–mediated lncRNA stabilization as the key mechanism by which lncRNAs are maintained at high levels. Our study lays the groundwork for understanding viral lncRNA–mediated regulation of host-virus interaction throughout the HCMV life cycle.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skin, Fibroblast

SUBMITTER: Sungwon Lee

LAB HEAD: Kwangseog Ahn

PROVIDER: PXD034587 | Pride | 2022-11-14

REPOSITORIES: Pride

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Functional and molecular dissection of HCMV long non-coding RNAs.

Lee Sungwon S Kim Hyewon H Hong Ari A Song Jaewon J Lee Sungyul S Kim Myeonghwan M Hwang Sung-Yeon SY Jeong Dongjoon D Kim Jeesoo J Son Ahyeon A Lee Young-Suk YS Kim V Narry VN Kim Jong-Seo JS Chang Hyeshik H Ahn Kwangseog K

Scientific reports 20221111 1

Small, compact genomes confer a selective advantage to viruses, yet human cytomegalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs); RNA1.2, RNA2.7, RNA4.9, and RNA5.0. Little is known about the function of these lncRNAs in the virus life cycle. Here, we dissected the functional and molecular landscape of HCMV lncRNAs. We found that HCMV lncRNAs occupy ~ 30% and 50-60% of total and poly(A)+viral transcriptome, respectively, throughout virus life cycle. RNA1.2, RNA2.7, and RNA4.9, the t ...[more]

PMID: 36369338

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