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Published on: October 21, 2012
Interaction of adenoviral E4 and E1b products in late gene expression
Abstract:
The adenovirus 294R protein of E4 ORF 6 forms a physical and functional complex with the 496R protein product of E1b. The E4 294R ORF 6 protein also functions in parallel with the E4 116R ORF 3 protein in viral late protein synthesis. We have examined the roles of these three proteins and the protein complex in viral late protein synthesis and late message metabolism, by comparing the phenotypes of E4 294R-, E4 116R-, and E1b 496R- mutants to those of a series of double mutants. Our data indicate that the 294R and 116R proteins act in parallel to permit the accumulation of normal levels of unprocessed late viral RNA in the nucleus of infected cells. Both 294R and 496R function in parallel with the 116R protein in viral nuclear RNA accumulation, but do so to different degrees, suggesting that 294R and 496R may have roles apart from the functional complex in mediating accumulation of viral messages in the nucleus, or that they have nonequivalent roles within the complex. Our results are also consistent with a role for the 496R/294R protein complex in mediating efficient transport of late messages from the nucleus to the cytoplasm and/or in maintaining the stability of those messages on reaching the cytoplasm, as suggested previously (S. Pilder, M. Moore, J. Logan, and T. Shenk, 1986, Mol. Cell. Biol. 6, 470-476). Finally the 116R protein seems to act in parallel with the complex to permit normal viral DNA replication.
Insights
Adenovirus E4 ORF 6 (294R) and E1b (496R) proteins form a complex crucial for viral RNA metabolism. These proteins, along with E4 ORF 3 (116R), regulate viral late protein synthesis and RNA nuclear accumulation.
Area of Science:
- * Virology
- * Molecular Biology
- * Gene Expression
Background:
- * Adenovirus E4 ORF 6 (294R) protein interacts with E1b (496R) protein.
- * E4 ORF 6 (294R) also functions with E4 ORF 3 (116R) in viral late protein synthesis.
Purpose of the Study:
- * To investigate the roles of E4 ORF 6 (294R), E1b (496R), and E4 ORF 3 (116R) proteins in viral late protein synthesis and RNA metabolism.
- * To compare the functions of individual mutants with double mutants to elucidate protein interactions and functions.
Main Methods:
- * Comparative analysis of single and double adenovirus mutants (E4 294R-, E4 116R-, E1b 496R-).
- * Phenotypic characterization of viral late protein synthesis and late message metabolism.
Main Results:
- * E4 (294R) and E4 (116R) proteins act in parallel to ensure normal accumulation of unprocessed viral RNA in the nucleus.
- * E4 (294R) and E1b (496R) proteins function with E4 (116R) in nuclear RNA accumulation, suggesting potential independent roles or nonequivalent functions within a complex.
- * The E1b (496R)/E4 (294R) complex may facilitate nuclear-cytoplasmic transport and/or cytoplasmic stability of late viral messages.
- * E4 (116R) acts in parallel with the E1b (496R)/E4 (294R) complex to enable normal viral DNA replication.
Conclusions:
- * Adenovirus E4 and E1b proteins play intricate, parallel roles in regulating viral RNA metabolism and replication.
- * The E1b (496R)/E4 (294R) complex is implicated in late message processing and transport.
- * E4 (116R) protein is essential for nuclear RNA accumulation and functions independently of the E1b (496R)/E4 (294R) complex in viral DNA replication.
