Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the mechanisms involved in the early-to-late RNA-processing switch which regulates the mRNA species generated from the adenovirus major late transcription unit (MLTU). In particular, polyadenylation choice mechanisms were characterized by using a reconstructed adenovirus E1A gene as a site for insertion of MLTU poly(A) regulation signals (L1 and L3). Adenovirus constructs containing the variant poly(A) recognition elements were used to compare E1A poly(A) signal utilization with wild-type MLTU (L1 to L5) utilization. In both early and late stages of infection, either polyadenylation site (L1 or L3) is capable of being utilized when presented as the only operational poly(A) site. In an early infection, a virus which contains multiple elements presented in tandem (L13) uses the first poly(A) site, L1, preferentially (ratio of L1 to L3, 8:1) in both E1A and MLTU loci. Transcription termination is not involved in restricting the utilization of the downstream L3 site. In a late infection, when each of the five MLTU poly(A) sites is used, a switch also occurs for the E1AL13 construct, with utilization of both the L1 and L3 poly(A) sites. The switch from early to late was not the result of altered processing factors in the late infection, as demonstrated by superinfecting the E1AL13 construct into cells which had already entered a late stage of infection. The superinfecting virus gave an L1-only phenotype; therefore, a cis mechanism is involved in adenovirus poly(A) regulation.
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PMID:Regulation of poly(A) site selection in adenovirus. 256 92

The transition from early to late stage infection by adenovirus involves a change in mRNA expression from the adenovirus major late transcription unit (AdMLTU). This early to late switch centers around alternative selection of one of five poly (A) sites (L1-L5) that code for the major structural proteins of Adenovirus. During the early stage of infection, steady state mRNA is primarily derived from the L1 poly (A) site. During the late stage of infection, each of the MLTU poly (A) sites is represented in the steady state mRNA pool (Falck-Pedersen, E., Logan, J., 1989. Regulation of poly(A) site selection in adenovirus. J. Virol. 63 (2), 532-541.). Using transient transfection of a plasmid expressing Chloramphenicol Acetyl Transferase with a tandem poly (A) minigene system (L13) (DeZazzo, J.D., Falck-Pedersen, E., Imperiale, M.J., 1991. Sequences regulating temporal poly(A) site switching in the adenovirus major late transcription unit. Mol. Cell. Biol. 11 (12), 5977-5984; Prescott, J., Falck-Pedersen, E., 1994. Sequence elements upstream of the 3' cleavage site confer substrate strength to the adenovirus L1 and L3 polyadenylation sites. Mol. Cell. Biol. 14 (7), 4682-4693.), it has been demonstrated that the promoter-proximal L1 poly (A) site which is poorly recognized by the 3' end processing machinery, contains an upstream repressor element (URE) that influences steady state levels of mRNA (Prescott, J.C., Liu, L., Falck-Pedersen, E., 1997. Sequence-mediated regulation of adenovirus gene expression by repression of mRNA accumulation. Mol. Cell. Biol. 17 (4), 2207-2216.). In this study, we have further characterized the elements that mediate L1URE function. These studies indicate that the L1 upstream regulatory element (L1 URE) contains a complex RNA architecture that serves to repress gene expression through multiple sub-effectors. The L1URE functions when located upstream of a heterologous poly (A) site, and is able to strongly suppress steady state mRNA expression from the MLTU L3 poly (A) site or the murine beta-globin poly (A) site. In the tandem L13 mini-gene system, the L1URE is revealed to influence steady state mRNA stability, and subdomains within L1URE influence both gene expression and the steady state ratio of transcripts processed at proximal versus distal poly (A) sites. Transcript and gene repression mediated by the L1URE may provide a general strategy employed by adenovirus to block premature expression of late stage MLTU transcripts.
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PMID:Characterization of an upstream regulatory element of adenovirus L1 poly (A) site. 1591 26