Cloning and characterization of a TFIIIC2 subunit (TFIIIC beta) whose presence correlates with activation of RNA polymerase III-mediated transcription by adenovirus E1A expression and serum factors.

Abstract

TFIIIC2 is a general factor essential for transcription of 5S RNA, tRNA, and VA RNA genes by mammalian RNA polymerase III and consists of two forms designated THIIC2a and TFIIIC2b. TFIIIC2a and TFIIIC2b share common subunits of 220, 102, 90, and 63 kD but differ with respect to transcription activity and the presence of a presumptive 110-kD subunit in the active form (TFIIIC2a). Because both forms can bind the promoter directly, a selective role for the 110-kD subunit in the regulation of RNA polymerase III activity has been suggested. To investigate this possibility, we have cloned and expressed a cDNA encoding the l l0-kD subunit (TFIIICB). Immunoprecipitation studies with anti-TFIIICI3 antibodies have confirmed that TFIIIC[3 is a bona fide subunit present only in TFIIIC2a, that TFIIIC2a and the general factor TFIIIC1 are associated in unfractionated extracts, and that previously undetected polypeptides (potential TFIIIC1 subunits) can be isolated in association with TFIIIC2a. Previous studies have shown that increases in RNA polymerase III activity during infection of cells by adenovirus (with concomitant E1A expression) or during cell growth at high serum concentration results from an increased activity in the TFIIIC fraction. Studies with antibodies to TFIIICB have shown that this is strongly correlated with a selective increase in the cellular concentration of the TFIIIC~ l l0-kD subunit and a concomitant rise in the ratio of the active-to-inactive forms of TFIIIC2.

Deregulation of RNA polymerase III transcription in cervical epithelium in response to high-risk human papillomavirus

“…Furthermore, adenoviral infection can selectively increase the level of TFIIIC110 (Sinn et al, 1995). This led us to wonder if TFIIIC2 might also be induced when cells are infected and transformed by HPV, but we found no evidence that this is the case.…”

Identification of an autonomously initiating RNA polymerase III holoenzyme containing a novel factor that is selectively inactivated during protein synthesis inhibition

“…) also indicate that human TFIIIB contains a third subunit with weak sequence relationships to the third (largest) subunit of yeast TFIIIB. Human TFIIIC1, which has no known counterpart in yeast, is less well characterized but stabilizes and extends promoter interactions of TFIIIC2 (for review, see Wang and Roeder 1996) and can interact with TFIIIC2 both in the absence and presence of promoter DNA (Sinn et al 1995;Z. Wang, and R.G.…”

“…Studies of these factors in various regulatory responses have shown that serum factors and early stage adenovirus infection stimulate RNA Pol III transcription by increasing the levels of the active form of TFIIIC2 (Sinn et al 1995), whereas transcription has been reported to be down-regulated through TFIIIB in differentiating mouse F9 embryonic carcinoma (EC) cells and during mitosis (Scott et al 1983;White et al 1989;Gottesfeld et al 1994). Transcription by RNA Pol III is also down-regulated in other situations, including growth into stationary phase (Tower and Sollner-Webb 1988), growth arrest induced by protein synthesis inhibitors (Gokal et al 1986), starvation for an essential nutrient (Hoeffler and Roeder 1985), and late-stage virus infection (Sö derlund et al 1976;Weinmann 1976).…”

Genes for human general transcription initiation factors TFIIIB, TFIIIB-associated proteins, TFIIIC2 and PTF/SNAPC: functional and positional candidates for tumour predisposition or inherited genetic diseases?

“…This inhibition may be reversed by viruses such as SV40, Hepatitis B virus and human T cell leukemia virus type 1 (White, 1998). SV40 large T Antigen, as well as serum stimulation or adenovirus infection, increase the amount of the 110 kDa subunit of TFIIIC2, thereby activating the factor and, accordingly, PolIII transcription (Sinn et al, 1995;Damania et al, 1998;Larminie et al, 1999). All TFIIIC2 subunits are overexpressed in ovarian tumours, a leading cause of gynecological cancer deaths in the USA (Winter et al, 2000).…”