Regulation of pol III transcription by nutrient and stress signaling pathways

Abstract

Transcription by RNA polymerase III (pol III) is responsible for ~15% of total cellular transcription through the generation of small structured RNAs such as tRNA and 5S RNA. The coordinate synthesis of these molecules with ribosomal protein mRNAs and rRNA couples the production of ribosomes and their tRNA substrates and balances protein synthetic capacity with the growth requirements of the cell. Ribosome biogenesis in general and pol III transcription in particular is known to be regulated by nutrient availability, cell stress and cell cycle stage and is perturbed in pathological states. High throughput proteomic studies have catalogued modifications to pol III subunits, assembly, initiation and accessory factors but most of these modifications have yet to be linked to functional consequences. Here we review our current understanding of the major points of regulation in the pol III transcription apparatus, the targets of regulation and the signaling pathways known to regulate their function.

Cytoskeletal Filamin A Differentially Modulates RNA Polymerase III Gene Transcription in Transformed Cell Lines

“…These RNA products account for about 15% of total cellular transcripts and are involved in the regulation of protein biogenesis, RNA splicing, protein transportation, and protein-coding gene transcription (1)(2)(3). In cancer, aberrant expression of pol III products strongly correlates with the transformed state (4 -6).…”

“…Eukaryotic RNA polymerase (pol) 3 III mediates the synthesis of many non-coding RNAs that include tRNA, 5S rRNA, U6 RNA, 7SL RNA, and other small RNAs. These RNA products account for about 15% of total cellular transcripts and are involved in the regulation of protein biogenesis, RNA splicing, protein transportation, and protein-coding gene transcription (1)(2)(3).…”

Comparative overview of RNA polymerase II and III transcription cycles, with focus on RNA polymerase III termination and reinitiation

“…On the genes with a hairpin ≥ 5 nt upstream of the T-tract, RNAP III would have to back up as part of termination but, as shown by the new data, without RNA 3′ end retraction. 13 The elongation rate for RNAP III on yeast 5S rRNA genes has been calculated to be 60-75 nt/s with an occupancy of 2-3 RNAP III molecules per 5S gene and a reinitiation interval of 1.2 s. 94 Calculations based on tRNA levels in yeast estimate the rate of RNA production, i.e., termination, at 2-4 transcripts/gene/s 95 (or a time between two successive terminating RNAP III molecules equal to 250-500 ms). To put it another way, an RNAP III molecule involved in tRNA production in fast growing yeast cells has only 0.25-0.5 s to terminate as it approaches the terminator.…”

tRN-A-RS Acts As Biomarker for Cancer and Other Diseases

“…Thus, TORC1 via RNA Pol III drives tissue and body growth during development. Another oncogene, Myc, directly localizes at tRNA genes by associating with the Brf component of the TFIIIB complex and recruits the histone modifying enzymes-GCN5 and TRRAP-to promote transcription [104]. The conserved Ras family of G-proteins, H-Ras, K-Ras and N-Ras, function as molecular switches that control cell growth, proliferation, survival, differentiation including stimulation of protein synthesis.…”