The nuclear and cytoplasmic activities of RNA polymerase III, and an evolving transcriptome for surveillance

Author:

Kessler Alan C1,Maraia Richard J1ORCID

Affiliation:

1. Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892 USA

Abstract

Abstract A 1969 report that described biochemical and activity properties of the three eukaryotic RNA polymerases revealed Pol III as highly distinguishable, even before its transcripts were identified. Now known to be the most complex, Pol III contains several stably-associated subunits referred to as built-in transcription factors (BITFs) that enable highly efficient RNA synthesis by a unique termination-associated recycling process. In vertebrates, subunit RPC7(α/β) can be of two forms, encoded by POLR3G or POLR3GL, with differential activity. Here we review promoter-dependent transcription by Pol III as an evolutionary perspective of eukaryotic tRNA expression. Pol III also provides nonconventional functions reportedly by promoter-independent transcription, one of which is RNA synthesis from DNA 3′-ends during repair. Another is synthesis of 5′ppp-RNA signaling molecules from cytoplasmic viral DNA in a pathway of interferon activation that is dysfunctional in immunocompromised patients with mutations in Pol III subunits. These unconventional functions are also reviewed, including evidence that link them to the BITF subunits. We also review data on a fraction of the human Pol III transcriptome that evolved to include vault RNAs and snaRs with activities related to differentiation, and in innate immune and tumor surveillance. The Pol III of higher eukaryotes does considerably more than housekeeping.

Funder

National Institute of Child Health and Human Development

U.S. Department of Health and Human Services

National Institutes of Health

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Publisher

Oxford University Press (OUP)

Subject

Genetics

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