Figure 5.

Nuclear Pol III and cy-Pol III have distinct activities in immune and other functions. The nuclear and cytoplasmic compartments are illustrated as separated by the curved dashed line. In the nucleus, Pol III transcribes ncRNA genes which go through gene-specific maturation events, including association with general and RNA-specific proteins. Removal of the 5′ppp occurs by the triphosphatase DUSP11, although other mechanisms are involved in shielding the 5′ppp end of nascent Pol III transcripts including binding by La and other proteins (see text). Some of the ncRNAs Pol III transcriptome activities in immune function are shown enclosed in green, including T cell priming by tRNAs, tRF generation from tRNA genes, RIG-I activation by 7SL/SRP RNA unshielding. Activities referred to as surveillance and cell identity involving the snaR and VtRNAs discussed in the text are also indicated. The dashed black arrows in the nuclear compartment indicate crosstalk with Pol II gene regulation such as snaR association with NF90/interleukin-3 factor and 7SK snRNA involvement in regulation of immune response genes. Furthermore, crosstalk to the Pol II transcriptome can occur via micro-RNAs generated after nuclear export of the parent vtRNAs and snaRs which can target mRNAs. In the cytoplasm, cy-Pol III transcribes A + T-rich DNA into a direct-activating RIG-I ligand, which signals through the mitochondrial-tethered MAVS, leading to Pol II-mediated transcriptional induction of IFN and ∼100 IFN-stimulated genes (ISGs). The insert lists general features of the contrasting Pol III transcription systems.