A Kaposi's Sarcoma Virus RNA Element That Increases the Nuclear Abundance of Intronless Transcripts

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2005 Apr 30

PMID 15861127

Citations 78

Authors

Nicholas K Conrad

Joan A Steitz

Affiliations

Soon will be listed here.

Abstract

The Kaposi's sarcoma-associated herpesvirus produces a 1077 nucleotide noncoding, polyadenylated, exclusively nuclear RNA called PAN that is highly expressed in lytically infected cells. We report that PAN contains a novel post-transcriptional element essential for its abundant accumulation. The element, PAN-ENE (PAN RNA expression and nuclear retention element), increases the efficiency of 3'-end formation in vivo and is sufficient to enhance RNA abundance from an otherwise inefficiently expressed intronless beta-globin construct. The PAN-ENE does not concomitantly increase the production of encoded protein. Rather, it retains the unspliced beta-globin mRNA in the nucleus. Tethering of export factors can override the nuclear retention of the PAN-ENE, supporting a mechanism whereby the PAN-ENE blocks assembly of an export-competent mRNP. The activities of the PAN-ENE are specific to intronless constructs, since inserting the PAN-ENE into a spliced beta-globin construct has no effect on mRNA abundance and does not affect localization. This is the first characterization of a cis-acting element that increases RNA abundance of intronless transcripts but inhibits assembly of an export-competent mRNP.

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References

Brodsky A, Silver P . Pre-mRNA processing factors are required for nuclear export. RNA. 2001; 6(12):1737-49. PMC: 1370044. DOI: 10.1017/s1355838200001059. View

Custodio N, Carvalho C, Condado I, Antoniou M, Blencowe B, Carmo-Fonseca M . In vivo recruitment of exon junction complex proteins to transcription sites in mammalian cell nuclei. RNA. 2004; 10(4):622-33. PMC: 1370553. DOI: 10.1261/rna.5258504. View

Dimaano C, Ullman K . Nucleocytoplasmic transport: integrating mRNA production and turnover with export through the nuclear pore. Mol Cell Biol. 2004; 24(8):3069-76. PMC: 381686. DOI: 10.1128/MCB.24.8.3069-3076.2004. View

Erkmann J, Kutay U . Nuclear export of mRNA: from the site of transcription to the cytoplasm. Exp Cell Res. 2004; 296(1):12-20. DOI: 10.1016/j.yexcr.2004.03.015. View

Masuyama K, Taniguchi I, Kataoka N, Ohno M . RNA length defines RNA export pathway. Genes Dev. 2004; 18(17):2074-85. PMC: 515286. DOI: 10.1101/gad.1216204. View

Jensen T, Boulay J, Olesen J, Colin J, Weyler M, Libri D . Modulation of transcription affects mRNP quality. Mol Cell. 2004; 16(2):235-44. DOI: 10.1016/j.molcel.2004.09.019. View

Gruss P, Lai C, Dhar R, Khoury G . Splicing as a requirement for biogenesis of functional 16S mRNA of simian virus 40. Proc Natl Acad Sci U S A. 1979; 76(9):4317-21. PMC: 411565. DOI: 10.1073/pnas.76.9.4317. View

Bendena W, Garbe J, Traverse K, Lakhotia S, Pardue M . Multiple inducers of the Drosophila heat shock locus 93D (hsr omega): inducer-specific patterns of the three transcripts. J Cell Biol. 1989; 108(6):2017-28. PMC: 2115608. DOI: 10.1083/jcb.108.6.2017. View

Collis P, Antoniou M, Grosveld F . Definition of the minimal requirements within the human beta-globin gene and the dominant control region for high level expression. EMBO J. 1990; 9(1):233-40. PMC: 551652. DOI: 10.1002/j.1460-2075.1990.tb08100.x. View

10.

Eckner R, Ellmeier W, Birnstiel M . Mature mRNA 3' end formation stimulates RNA export from the nucleus. EMBO J. 1991; 10(11):3513-22. PMC: 453080. DOI: 10.1002/j.1460-2075.1991.tb04915.x. View

11.

Huang J, Liang T . A novel hepatitis B virus (HBV) genetic element with Rev response element-like properties that is essential for expression of HBV gene products. Mol Cell Biol. 1993; 13(12):7476-86. PMC: 364819. DOI: 10.1128/mcb.13.12.7476-7486.1993. View

12.

Gilmartin G, Fleming E, Oetjen J, Graveley B . CPSF recognition of an HIV-1 mRNA 3'-processing enhancer: multiple sequence contacts involved in poly(A) site definition. Genes Dev. 1995; 9(1):72-83. DOI: 10.1101/gad.9.1.72. View

13.

Huang Z, Yen T . Role of the hepatitis B virus posttranscriptional regulatory element in export of intronless transcripts. Mol Cell Biol. 1995; 15(7):3864-9. PMC: 230626. DOI: 10.1128/MCB.15.7.3864. View

14.

Liu X, Mertz J . HnRNP L binds a cis-acting RNA sequence element that enables intron-dependent gene expression. Genes Dev. 1995; 9(14):1766-80. DOI: 10.1101/gad.9.14.1766. View

15.

Moreira A, Wollerton M, MONKS J, Proudfoot N . Upstream sequence elements enhance poly(A) site efficiency of the C2 complement gene and are phylogenetically conserved. EMBO J. 1995; 14(15):3809-19. PMC: 394455. DOI: 10.1002/j.1460-2075.1995.tb00050.x. View

16.

Liu X, Mertz J . Sequence of the polypyrimidine tract of the 3'-terminal 3' splicing signal can affect intron-dependent pre-mRNA processing in vivo. Nucleic Acids Res. 1996; 24(9):1765-73. PMC: 145838. DOI: 10.1093/nar/24.9.1765. View

17.

Huang Y, Carmichael G . Role of polyadenylation in nucleocytoplasmic transport of mRNA. Mol Cell Biol. 1996; 16(4):1534-42. PMC: 231138. DOI: 10.1128/MCB.16.4.1534. View

18.

Zhong W, Wang H, Herndier B, Ganem D . Restricted expression of Kaposi sarcoma-associated herpesvirus (human herpesvirus 8) genes in Kaposi sarcoma. Proc Natl Acad Sci U S A. 1996; 93(13):6641-6. PMC: 39079. DOI: 10.1073/pnas.93.13.6641. View

19.

Sun R, Lin S, Gradoville L, Miller G . Polyadenylylated nuclear RNA encoded by Kaposi sarcoma-associated herpesvirus. Proc Natl Acad Sci U S A. 1996; 93(21):11883-8. PMC: 38153. DOI: 10.1073/pnas.93.21.11883. View

20.

Zhong W, Ganem D . Characterization of ribonucleoprotein complexes containing an abundant polyadenylated nuclear RNA encoded by Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8). J Virol. 1997; 71(2):1207-12. PMC: 191174. DOI: 10.1128/JVI.71.2.1207-1212.1997. View