Nuclease Escape Elements Protect Messenger RNA Against Cleavage by Multiple Viral Endonucleases

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2017 Aug 26

PMID 28841715

Citations 21

Authors

Mandy Muller

Britt A Glaunsinger

Affiliations

Soon will be listed here.

Abstract

During lytic Kaposi's sarcoma-associated herpesvirus (KSHV) infection, the viral endonu- clease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs, including the transcript encoding interleukin-6 (IL-6), escape SOX-induced cleavage. IL-6 escape is mediated through a 3' UTR RNA regulatory element that overrides the SOX targeting mechanism. Here, we reveal that this protective RNA element functions to broadly restrict cleavage by a range of homologous and non-homologous viral endonucleases. However, it does not impede cleavage by cellular endonucleases. The IL-6 protective sequence may be representative of a larger class of nuclease escape elements, as we identified a similar protective element in the GADD45B mRNA. The IL-6 and GADD45B-derived elements display similarities in their sequence, putative structure, and several associated RNA binding proteins. However, the overall composition of their ribonucleoprotein complexes appears distinct, leading to differences in the breadth of nucleases restricted. These findings highlight how RNA elements can selectively control transcript abundance in the background of widespread virus-induced mRNA degradation.

Citing Articles

Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.

SoRelle E, Haynes L, Willard K, Chang B, Chng J, Christofk H PLoS Pathog. 2024; 20(10):e1012341.

PMID: 39446925 PMC: 11563402. DOI: 10.1371/journal.ppat.1012341.

Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.

SoRelle E, Haynes L, Willard K, Chang B, Chng J, Christofk H bioRxiv. 2024; .

PMID: 38915538 PMC: 11195279. DOI: 10.1101/2024.06.14.598975.

A Balancing Act: The Viral-Host Battle over RNA Binding Proteins.

Bermudez Y, Hatfield D, Muller M Viruses. 2024; 16(3).

PMID: 38543839 PMC: 10974049. DOI: 10.3390/v16030474.

Mechanisms and consequences of mRNA destabilization during viral infections.

Shehata S, Watkins J, Burke J, Parker R Virol J. 2024; 21(1):38.

PMID: 38321453 PMC: 10848536. DOI: 10.1186/s12985-024-02305-1.

Interferon induced circRNAs escape herpesvirus host shutoff and suppress lytic infection.

Dremel S, Tagawa T, Koparde V, Hernandez-Perez C, Arbuckle J, Kristie T EMBO Rep. 2024; 25(3):1541-1569.

PMID: 38263330 PMC: 10933408. DOI: 10.1038/s44319-023-00051-z.

References

Schoenberg D, Maquat L . Regulation of cytoplasmic mRNA decay. Nat Rev Genet. 2012; 13(4):246-59. PMC: 3351101. DOI: 10.1038/nrg3160. View

Muller M, Hutin S, Marigold O, Li K, Burlingame A, Glaunsinger B . A ribonucleoprotein complex protects the interleukin-6 mRNA from degradation by distinct herpesviral endonucleases. PLoS Pathog. 2015; 11(5):e1004899. PMC: 4428876. DOI: 10.1371/journal.ppat.1004899. View

Hutin S, Lee Y, Glaunsinger B . An RNA element in human interleukin 6 confers escape from degradation by the gammaherpesvirus SOX protein. J Virol. 2013; 87(8):4672-82. PMC: 3624381. DOI: 10.1128/JVI.00159-13. View

Esclatine A, Taddeo B, Evans L, Roizman B . The herpes simplex virus 1 UL41 gene-dependent destabilization of cellular RNAs is selective and may be sequence-specific. Proc Natl Acad Sci U S A. 2004; 101(10):3603-8. PMC: 373509. DOI: 10.1073/pnas.0400354101. View

Schoenberg D . Mechanisms of endonuclease-mediated mRNA decay. Wiley Interdiscip Rev RNA. 2011; 2(4):582-600. PMC: 3347869. DOI: 10.1002/wrna.78. View

Peuchmaur M, Devergne O, Audouin J, Raphael M, Van Damme J, Galanaud P . Interleukin-6 gene expression in Castleman's disease. Blood. 1991; 78(11):2923-30. View

Glaunsinger B, Ganem D . Highly selective escape from KSHV-mediated host mRNA shutoff and its implications for viral pathogenesis. J Exp Med. 2004; 200(3):391-8. PMC: 2211977. DOI: 10.1084/jem.20031881. View

SMILEY J, Elgadi M, Saffran H . Herpes simplex virus vhs protein. Methods Enzymol. 2001; 342:440-51. DOI: 10.1016/s0076-6879(01)42565-1. View

Parrish S, Moss B . Characterization of a vaccinia virus mutant with a deletion of the D10R gene encoding a putative negative regulator of gene expression. J Virol. 2005; 80(2):553-61. PMC: 1346865. DOI: 10.1128/JVI.80.2.553-561.2006. View

10.

Sin S, Roy D, Wang L, Staudt M, Fakhari F, Patel D . Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling. Blood. 2006; 109(5):2165-73. PMC: 1801055. DOI: 10.1182/blood-2006-06-028092. View

11.

Rivas H, Schmaling S, Gaglia M . Shutoff of Host Gene Expression in Influenza A Virus and Herpesviruses: Similar Mechanisms and Common Themes. Viruses. 2016; 8(4):102. PMC: 4848596. DOI: 10.3390/v8040102. View

12.

Abernathy E, Clyde K, Yeasmin R, Krug L, Burlingame A, Coscoy L . Gammaherpesviral gene expression and virion composition are broadly controlled by accelerated mRNA degradation. PLoS Pathog. 2014; 10(1):e1003882. PMC: 3894220. DOI: 10.1371/journal.ppat.1003882. View

13.

Chandriani S, Ganem D . Host transcript accumulation during lytic KSHV infection reveals several classes of host responses. PLoS One. 2007; 2(8):e811. PMC: 1950738. DOI: 10.1371/journal.pone.0000811. View

14.

Barzilai A, Zivony-Elbom I, Sarid R, Noah E, Frenkel N . The herpes simplex virus type 1 vhs-UL41 gene secures viral replication by temporarily evading apoptotic cellular response to infection: Vhs-UL41 activity might require interactions with elements of cellular mRNA degradation machinery. J Virol. 2005; 80(1):505-13. PMC: 1317524. DOI: 10.1128/JVI.80.1.505-513.2006. View

15.

Paschoud S, Dogar A, Kuntz C, Grisoni-Neupert B, Richman L, Kuhn L . Destabilization of interleukin-6 mRNA requires a putative RNA stem-loop structure, an AU-rich element, and the RNA-binding protein AUF1. Mol Cell Biol. 2006; 26(22):8228-41. PMC: 1636780. DOI: 10.1128/MCB.01155-06. View

16.

Zhang Y, Bhatia D, Xia H, Castranova V, Shi X, Chen F . Nucleolin links to arsenic-induced stabilization of GADD45alpha mRNA. Nucleic Acids Res. 2006; 34(2):485-95. PMC: 1342039. DOI: 10.1093/nar/gkj459. View

17.

Oishi K, Yamayoshi S, Kawaoka Y . Mapping of a Region of the PA-X Protein of Influenza A Virus That Is Important for Its Shutoff Activity. J Virol. 2015; 89(16):8661-5. PMC: 4524237. DOI: 10.1128/JVI.01132-15. View

18.

Elgadi M, Hayes C, SMILEY J . The herpes simplex virus vhs protein induces endoribonucleolytic cleavage of target RNAs in cell extracts. J Virol. 1999; 73(9):7153-64. PMC: 104239. DOI: 10.1128/JVI.73.9.7153-7164.1999. View

19.

Kamitani W, Huang C, Narayanan K, Lokugamage K, Makino S . A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein. Nat Struct Mol Biol. 2009; 16(11):1134-40. PMC: 2784181. DOI: 10.1038/nsmb.1680. View

20.

Santarelli R, Gonnella R, Di Giovenale G, Cuomo L, Capobianchi A, Granato M . STAT3 activation by KSHV correlates with IL-10, IL-6 and IL-23 release and an autophagic block in dendritic cells. Sci Rep. 2014; 4:4241. PMC: 3937791. DOI: 10.1038/srep04241. View