Date of Award


Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Steitz, Joan A.


Marmoset T lymphocytes transformed by herpesvirus saimiri contain the first virally encoded U RNAs (called HSURs) to be identified. HSURs assemble into small nuclear ribonucleoproteins (snRNPs) of low abundance ($<$2 $\times$ 10$\sp4$ copies/cell). They bind proteins with Sm determinants and acquire a 5$\sp\prime$ trimethylguanosine cap structure. The sequences of HSUR 1 (143 nucleotides), HSUR 2 (115 nucleotides), HSUR 3 (76 nucleotides) HSUR 4 (106 nucleotides) and HSUR 5 (111-114 nucleotides) are related to each other but distinct from any previously characterized cellular U RNA. The viral genes encoding the HSURs possess conserved enhancer, promoter and 3$\sp\prime$ end formation signals unique to U RNA genes.The levels of HSURs 1-4 in HeLa transient expression systems are comparable to those found in virally transformed T cells (23%-91%). In contrast, HSUR 5 is expressed at nine-fold higher levels in transfected HeLa cells. HSURs expressed in transfected cells bind proteins with Sm determinants and acquire a 5$\sp\prime$ trimethylguanosine cap structure, as in transformed T cells. HSUR 1 or HSUR 4 particles from transfected HeLa cells migrate between 10S and 15S in velocity gradients, identical to the sedimentation of "monoparticles" produced in virally transformed lymphocytes. We conclude from these transfection experiments that no other herpesvirus saimiri or lymphocyte specific gene products appear to be required for efficient expression of the HSUR genes or for subsequent assembly of the viral U RNAs into snRNP particles.The stretch of similar sequences found on the 5$\sp\prime$ ends HSUR 1, HSUR 2, and HSUR 5 are AU-rich and contain 1-3 repeats of the AUUUA sequence motif. These AU-rich sequences have been identified as mRNA destabilization signals which specify rapid degradation of the transiently expressed mRNAs (Shaw and Kamen, 1986). Because HSURs are estimated to be in 100-1000 fold more abundant than any mRNA, they could stabilize these short-lived transcripts by competitively binding and inhibiting the factor(s) that recognize the mRNA destabilization signal. The resulting overexpression of cellular growth factors could contribute to the transforming ability of herpesvirus saimiri. (Abstract shortened with permission of author.)

Open Access

This Article is Open Access