Structural and functional analysis of the avian leukemia virus constitutive transport element

Yang, Jin; Cullen, Bryan R.

doi:10.1017/s1355838299991616

Cited by 34 publications

(45 citation statements)

References 31 publications

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“…In addition to splicing enhancers and repressors, there are also RNA sequence elements that allow transport of unspliced RNAs to the cytoplasm (261)(262)(263)(264)(265). Some of these transport elements are constitutive, interacting directly with cellular factors (266)(267)(268)(269)(270)(271). Other elements interact with viral proteins, such as HIV Rev, to allow viral control of the nuclear export process (264).…”

Section: Retroviral Splicing and The Balance Of Splicing And Transportmentioning

confidence: 99%

Mechanisms of Alternative Pre-Messenger RNA Splicing

Black

2003

Annu. Rev. Biochem.

2,346

2,227

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Alternative pre-mRNA splicing is a central mode of genetic regulation in higher eukaryotes. Variability in splicing patterns is a major source of protein diversity from the genome. In this review, I describe what is currently known of the molecular mechanisms that control changes in splice site choice. I start with the best-characterized systems from the Drosophila Sex Determination pathway, and then describe the regulators of other systems about whose mechanisms there is some data. How these regulators are combined into complex systems of tissue specific splicing is discussed. In conclusion, very recent studies are presented that point to new directions for understanding alternative splicing and its mechanisms.

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Section: Retroviral Splicing and The Balance Of Splicing And Transportmentioning

confidence: 99%

Mechanisms of Alternative Pre-Messenger RNA Splicing

Black

2003

Annu. Rev. Biochem.

2,346

2,227

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“…Furthermore, as reported previously (35) and confirmed in our experiments (unpublished observation), DR deletion does not impart any effect on the RSV replication in rodent cells. On the other hand, it was demonstrated that DR facilitates gRNA egress from the nucleus in mammalian cells (42). Still, there remains the possibility that rodent cells are devoid of some factor(s) needed for interaction with DRs or produce an inhibitor paralyzing DR function, especially at later stages of gRNA processing that follow its export.…”

Section: Discussionmentioning

confidence: 99%

Molecular Events Accompanying Rous Sarcoma Virus Rescue from Rodent Cells and the Role of Viral Gene Complementation

Lounková

Dráberová

Šenigl

et al. 2014

J Virol

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Transformation of rodent cells with avian Rous sarcoma virus (RSV) opened new ways to studying virus integration and expression in nonpermissive cells. We were interested in (i) the molecular changes accompanying fusion of RSV-transformed mammalian cells with avian cells leading to virus rescue and (ii) enhancement of this process by retroviral gene products. The RSV-transformed hamster RSCh cell line was characterized as producing only a marginal amount of env mRNA, no envelope glycoprotein, and a small amount of unprocessed Gag protein. Egress of viral unspliced genomic RNA from the nucleus was hampered, and its stability decreased. Cell fusion of the chicken DF-1 cell line with RSCh cells led to production of env mRNA, envelope glycoprotein, and processed Gag and virus-like particle formation. Proteosynthesis inhibition in DF-1 cells suppressed steps leading to virus rescue. Furthermore, new aberrantly spliced env mRNA species were found in the RSCh cells. Finally, we demonstrated that virus rescue efficiency can be significantly increased by complementation with the env gene and the highly expressed gag gene and can be increased the most by a helper virus infection. In summary, Env and Gag synthesis is increased after RSV-transformed hamster cell fusion with chicken fibroblasts, and both proteins provided in trans enhance RSV rescue. We conclude that the chicken fibroblast yields some factor(s) needed for RSV replication, particularly Env and Gag synthesis, in nonpermissive rodent cells. IMPORTANCE One of the important issues in retrovirus heterotransmission is related to cellular factors that prevent virus replication. Rous sarcoma virus (RSV), a member of the avian sarcoma and leukosis family of retroviruses, is able to infect and transform mammalian cells; however, such transformed cells do not produce infectious virus particles.Using the well-defined model of RSVtransformed rodent cells, we established that the lack of virus replication is due to the absence of chicken factor(s), which can be supplemented by cell fusion. Cell fusion with permissive chicken cells led to an increase in RNA splicing and nuclear export of specific viral mRNAs, as well as synthesis of respective viral proteins and production of virus-like particles. RSV rescue by cell fusion can be potentiated by in trans expression of viral genes in chicken cells. We conclude that rodent cells lack some chicken factor(s) required for proper viral RNA processing and viral protein synthesis.

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“…Using bioinformatic tools, we have not been able to find any genes outside of the NXF family that possess CTEs based on sequence homology. However, the genomes of several mammalian and endogenous retroviruses have been shown to contain non-homologous elements that function as CTEs in conjunction with Nxf1/Nxt (Ogert and Beemon 1995;Yang and Cullen 1999;Nappi et al 2001;Legiewicz et al 2010;Sakuma et al 2014). In addition, we have previously used retroviral vector "trap" strategies to identify several host cell CTEs that lack apparent homology with the MPMV/NXF1 CTE, but which still function in conjunction with Nxf1/Nxt1 .…”

Section: Nxf1-cte Functional Conservationmentioning

confidence: 99%

Evolutionary conservation of a molecular machinery for export and expression of mRNAs with retained introns

Wang

Rekosh

Hammarskjöld

2015

RNA

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Intron retention is one of the least studied forms of alternative splicing. Through the use of retrovirus and other model systems, it was established many years ago that mRNAs with retained introns are subject to restriction both at the level of nucleocytoplasmic export and cytoplasmic expression. It was also demonstrated that specific cis-acting elements in the mRNA could serve to bypass these restrictions. Here we show that one of these elements, the constitutive transport element (CTE), first identified in the retrovirus MPMV and subsequently in the human NXF1 gene, is a highly conserved element. Using GERP analysis, CTEs with strong primary sequence homology, predicted to display identical secondary structure, were identified in NXF genes from >30 mammalian species. CTEs were also identified in the predicted NXF1 genes of zebrafish and coelacanths. The CTE from the zebrafish NXF1 was shown to function efficiently to achieve expression of mRNA with a retained intron in human cells in conjunction with zebrafish Nxf1 and cofactor Nxt proteins. This demonstrates that all essential functional components for expression of mRNA with retained introns have been conserved from fish to man.

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Structural and functional analysis of the avian leukemia virus constitutive transport element

Cited by 34 publications

References 31 publications

Mechanisms of Alternative Pre-Messenger RNA Splicing

Mechanisms of Alternative Pre-Messenger RNA Splicing

Molecular Events Accompanying Rous Sarcoma Virus Rescue from Rodent Cells and the Role of Viral Gene Complementation

Evolutionary conservation of a molecular machinery for export and expression of mRNAs with retained introns

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