Analysis of splice sites in the early region of bovine polyomavirus: evidence for a unique pattern of large T mRNA splicing

Schuurman, Rob; Jacobs, Marcel V.; Strien, A. van; Noordaa, J. van der; Sol, C. J. A.

doi:10.1099/0022-1317-73-11-2879

Cited by 6 publications

(5 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown, the antibody was capable of detecting a protein with an apparent Mr of about 70K expressed in ME-RBPy-3 cells, but not in untransformed mouse cells or in SV40-transformed murine cells. The size of this protein corresponds very well with the predicted size of BPyV large T antigen, as proposed by Schuurman et al (1990Schuurman et al ( , 1992.…”

Section: An Indication Of the Integrity Of The Early Region Of Bpyv Wsupporting

confidence: 83%

Bovine polyomavirus, a cell-transforming virus with tumorigenic potential

Schuurman

Strien²,

Steenis³

et al. 1992

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

Section: An Indication Of the Integrity Of The Early Region Of Bpyv Wsupporting

confidence: 83%

Bovine polyomavirus, a cell-transforming virus with tumorigenic potential

Schuurman

Strien²,

Steenis³

et al. 1992

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

“…However, the short half-life of tiny T antigen and its failure to accumulate in cells suggest that it is a "disposable" domain: its capacity to compete for binding of the cellular partners of the small, middle, and large T antigens might even reduce the vigor of the viral replication cycle. Reports of short-lived SV40 and bovine polyomavirus T antigens containing the common amino-terminal domain have also been made, but their functions have not been defined (61,66,85).…”

Section: Discussionmentioning

confidence: 99%

Tiny T antigen: an autonomous polyomavirus T antigen amino-terminal domain

Riley

Yoo

Mda

et al. 1997

J Virol

View full text Add to dashboard Cite

Three mRNAs from the murine polyomavirus early region encode the three well-characterized tumor antigens. We report the existence of a fourth alternatively spliced mRNA which encodes a fourth tumor antigen, tiny T antigen, which comprises the amino-terminal domain common to all of the T antigens but is extended by six unique amino acid residues. The amount of tiny T antigen in infected cells is small because of its short half-life. Tiny T antigen stimulates the ATPase activity of Hsc70, most likely because of its DnaJ-like motif. The common amino-terminal domain may interface with chaperone complexes to assist the T antigens in carrying out their diverse functions of replication, transcription, and transformation in the appropriate cellular compartments. The small, middle, and large T antigens expressed by the murine polyomavirus (muPy) are formed of a common aminoterminal sequence juxtaposed to unique carboxy-terminal sequences (33, 65). Such parsimony in protein structures reflects the pattern of viral gene expression, for the T antigens are encoded by a single primary transcript containing two splice acceptor and two splice donor sites (76) (Fig. 1), creating the potential of four separate mRNAs. Three of these RNAs encode the small, middle, and large T antigens. The fourth mRNA, heretofore undetected, should encode a protein with the T antigen common amino-terminal domain extended by six residues. Here, we report the detection of this mRNA and the partial characterization of the protein it encodes (tiny T antigen). Genetic and biochemical evidence indicates the muPy T antigen common amino-terminal domain is required for cell transformation and promotes small and middle T antigen association with PP2A, c-Src, and perhaps other proteins (5, 26, 73). These cellular signal transducers strongly influence viral DNA replication, transcription, and translation; consequently, the T antigen common amino-terminal domain must contribute to virtually all aspects of the virus life cycle. Sequence homology between the T antigen amino-terminal domain and DnaJ proteins has been noted (36). DnaJ proteins modulate the ATPase activity of the hsp70 class of chaperones, and we observe that tiny T antigen expressed in Escherichia coli and purified to near homogeneity exhibits such a stimulatory activity in vitro. This activity within the T antigen amino-terminal domain very likely contributes to the functions of the T antigens by promoting their interactions with cellular chaperones. MATERIALS AND METHODS Cells and viruses. NIH 3T3, 3T6, and COS1 cells were obtained from the American Type Culture Collection. Polyomavirus transformed MOP-3T3 and MOP-3T6 cells were obtained from John Hassell (McMaster University, Ontario, Canada). Whole mouse embryo (WME) cells were prepared from outbred mice as described previously (24). All cells were grown in Dulbecco's modified Eagle's medium (low glucose) supplemented with 10% fetal calf serum.

show abstract

“…The important PP2A binding domain (as mentioned below) of ST is made only upon splicing out the second intron (and not the first from an unusual LT with two introns), which appears to show how evolution could have produced ST (although bovines do not appear to normally produce this protein). However, sequences coding for MT are still a mystery since they do not appear until late in the rodent lineage (303). Interestingly, the polyomaviruses that have LT proteins without the carboxyterminal domain are those that encode an MT.…”

Section: Origins Of Middle T Antigen An Evolutionary Conundrummentioning

confidence: 99%

Natural Biology of Polyomavirus Middle T Antigen

Gottlieb

Villarreal

2001

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

“It has been commented by someone that ‘polyoma’ is an adjective composed of a prefix and suffix, with no root between—a meatless linguistic sandwich” (C. J. Dawe). The very name “polyomavirus” is a vague mantel: a name given before our understanding of these viral agents was clear but implying a clear tumor life-style, as noted by the late C. J. Dawe. However, polyomavirus are not by nature tumor-inducing agents. Since it is the purpose of this review to consider the natural function of middle T antigen (MT), encoded by one of the seemingly crucial transforming genes of polyomavirus, we will reconsider and redefine the virus and its MT gene in the context of its natural biology and function. This review was motivated by our recent in vivo analysis of MT function. Using intranasal inoculation of adult SCID mice, we have shown that polyomavirus can replicate with an MT lacking all functions associated with transformation to similar levels to wild-type virus. These observations, along with an almost indistinguishable replication of all MT mutants with respect to wild-type viruses in adult competent mice, illustrate that MT can have a play subtle role in acute replication and persistence. The most notable effect of MT mutants was in infections of newborns, indicating that polyomavirus may be highly adapted to replication in newborn lungs. It is from this context that our current understanding of this well-studied virus and gene is presented

show abstract

Analysis of splice sites in the early region of bovine polyomavirus: evidence for a unique pattern of large T mRNA splicing

Cited by 6 publications

References 27 publications

Bovine polyomavirus, a cell-transforming virus with tumorigenic potential

Bovine polyomavirus, a cell-transforming virus with tumorigenic potential

Tiny T antigen: an autonomous polyomavirus T antigen amino-terminal domain

Natural Biology of Polyomavirus Middle T Antigen

Contact Info

Product

Resources

About