In eukaryote cells, RNA polymerase III (also called Pol III) is a protein that transcribes DNA to synthesize ribosomal 5S

rRNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosoma ...

tRNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...

and other small RNAs. The genes transcribed by RNA Pol III fall in the category of "housekeeping" genes whose expression is required in all cell types and most environmental conditions. Therefore, the regulation of Pol III transcription is primarily tied to the regulation of

cell growth Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than ...

and the

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

, thus requiring fewer regulatory proteins than

RNA polymerase II RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryoti ...

. Under stress conditions however, the protein Maf1 represses Pol III activity.

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is another Pol III inhibitor via its direct target TOR.

Transcription

The process of

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

(by any polymerase) involves three main stages: *Initiation, requiring construction of the RNA polymerase complex on the gene's promoter *Elongation, the synthesis of the RNA transcript *Termination, the finishing of RNA transcription and disassembly of the RNA polymerase complex

Initiation

Initiation: the construction of the polymerase complex on the promoter. Pol III is unusual (compared to Pol II) by requiring no control sequences upstream of the gene, instead normally relying on internal control sequences - sequences within the transcribed section of the gene (although upstream sequences are occasionally seen, e.g. U6 snRNA gene has an upstream

TATA box In molecular biology, the TATA box (also called the Goldberg–Hogness box) is a sequence of DNA found in the core promoter region of genes in archaea and eukaryotes. The bacterial homolog of the TATA box is called the Pribnow box which has ...

as seen in Pol II Promoters). There are three classes of Pol III initiation, corresponding to 5S rRNA, tRNA, and U6 snRNA initiation. In all cases, the process starts with transcription factors binding to control sequences, and ends with TFIIIB (Transcription Factor for polymerase III B) being recruited to the complex and assembling Pol III. TFIIIB consists of three subunits:

TATA binding protein The TATA-binding protein (TBP) is a general transcription factor that binds specifically to a DNA sequence called the TATA box. This DNA sequence is found about 30 base pairs upstream of the transcription start site in some eukaryotic gene p ...

(TBP), a TFIIB-related factor ( BRF1, or BRF2 for transcription of a subset of Pol III-transcribed genes in vertebrates), and a B-double-prime ( BDP1) unit. The overall architecture bears similarities to that of Pol II.

Class I

''Typical stages in 5S rRNA (also termed class I) gene initiation:'' * TFIIIA (Transcription Factor for polymerase III A) binds to the intragenic (lying within the transcribed DNA sequence) 5S rRNA control sequence, the C Block (also termed box C). *TFIIIA serves as a platform that replaces the A and B Blocks for positioning TFIIIC in an orientation with respect to the start site of transcription that is equivalent to what is observed for tRNA genes. *Once TFIIIC is bound to the TFIIIA-DNA complex, the assembly of TFIIIB proceeds as described for tRNA transcription.

Class II

''Typical stages in a

(also termed class II) gene initiation:'' * TFIIIC (Transcription Factor for polymerase III C) binds to two intragenic (lying within the transcribed DNA sequence) control sequences, the A and B Blocks (also termed box A and box B). *TFIIIC acts as an assembly factor that positions TFIIIB to bind to DNA at a site centered approximately 26 base pairs upstream of the start site of transcription. *TFIIIB is the transcription factor that assembles Pol III at the start site of transcription. Once TFIIIB is bound to DNA, TFIIIC is no longer required. TFIIIB also plays an essential role in promoter opening.

Class III

''Typical stages in a

U6 snRNA U6 snRNA is the non-coding small nuclear RNA (snRNA) component of U6 snRNP (''small nuclear ribonucleoprotein''), an RNA-protein complex that combines with other snRNPs, unmodified pre-mRNA, and various other proteins to assemble a spliceosome, ...

(also termed class III) gene initiation (documented in vertebrates only):'' * SNAPc (SNRNA Activating Protein complex; subunits: 1, 2, 3, 4, 5) (also termed PBP and PTF) binds to the PSE (Proximal Sequence Element) centered approximately 55 base pairs upstream of the start site of transcription. This assembly is greatly stimulated by the Pol II transcription factors Oct1 and STAF that bind to an enhancer-like DSE (Distal Sequence Element) at least 200 base pairs upstream of the start site of transcription. These factors and promoter elements are shared between Pol II and Pol III transcription of snRNA genes. * SNAPc acts to assemble TFIIIB at a TATA box centered 26 base pairs upstream of the start site of transcription. It is the presence of a TATA box that specifies that the snRNA gene is transcribed by Pol III rather than Pol II. *The TFIIIB for U6 snRNA transcription contains a smaller Brf1 paralogue, Brf2. *TFIIIB is the transcription factor that assembles Pol III at the start site of transcription. Sequence conservation predicts that TFIIIB containing Brf2 also plays a role in promoter opening.

Elongation

TFIIIB remains bound to DNA following initiation of transcription by Pol III (unlike bacterial σ factors and most of the basal transcription factors for Pol II transcription). This leads to a high rate of transcriptional reinitiation of Pol III-transcribed genes.

Termination

Polymerase III terminates transcription at small polyUs stretch (5-6). In eukaryotes, a

hairpin loop Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence wh ...

is not required, but may enhance termination efficiency in humans.

Transcribed RNAs

The types of RNAs transcribed from RNA polymerase III include: *

Transfer RNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...

s * 5S ribosomal RNA *

U6 spliceosomal RNA U6 snRNA is the non-coding small nuclear RNA (snRNA) component of U6 snRNP (''small nuclear ribonucleoprotein''), an RNA-protein complex that combines with other snRNPs, unmodified pre-mRNA, and various other proteins to assemble a spliceosome, ...

RNase P Ribonuclease P (, ''RNase P'') is a type of ribonuclease which cleaves RNA. RNase P is unique from other RNases in that it is a ribozyme – a ribonucleic acid that acts as a catalyst in the same way that a protein-based enzyme would. Its f ...

and

RNase MRP RNase MRP (also called RMRP) is an enzymatically active ribonucleoprotein with two distinct roles in eukaryotes. RNAse MRP stands for RNAse for mitochondrial RNA processing. In mitochondria it plays a direct role in the initiation of mitochondria ...

RNA *

7SL RNA The signal recognition particle RNA, (also known as 7SL, 6S or 4.5S RNA) is part of the signal recognition particle (SRP) ribonucleoprotein complex. SRP recognizes the signal peptide and binds to the ribosome, halting protein synthesis. Signal re ...

(the RNA component of the

signal recognition particle The signal recognition particle (SRP) is an abundant, cytosolic, universally conserved ribonucleoprotein (protein- RNA complex) that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membr ...

) *

Vault RNA Many eukaryotic cells contain large ribonucleoprotein particles in the cytoplasm known as vaults. The vault complex comprises the major vault protein (MVP), two minor vault proteins ( VPARP and TEP1), and a variety of small untranslated RNA mol ...

s *

Y RNA Y RNAs are small non-coding RNAs. They are components of the Ro60 ribonucleoprotein particle which is a target of autoimmune antibodies in patients with systemic lupus erythematosus. They are also reported to be necessary for DNA replication thr ...

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(short interspersed repetitive elements) *

7SK RNA In molecular biology 7SK is an abundant small nuclear RNA found in metazoans. It plays a role in regulating transcription by controlling the positive transcription elongation factor P-TEFb. 7SK is found in a small nuclear ribonucleoprotein c ...

*Several

microRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...

s *Several small nucleolar RNAs *Several gene regulatory antisense RNAs

Role in DNA repair

RNA polymerase III appears to be essential for

homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...

al repair of DNA double-strand breaks.Liu S, Hua Y, Wang J, Li L, Yuan J, Zhang B, Wang Z, Ji J, Kong D. RNA polymerase III is required for the repair of DNA double-strand breaks by homologous recombination. Cell. 2021 Mar 4;184(5):1314-1329.e10. doi: 10.1016/j.cell.2021.01.048. Epub 2021 Feb 23. PMID: 33626331 RNA polymerase III catalyzes formation of a transient RNA-DNA hybrid at double strand breaks, an essential intermediate step in homologous recombination mediated double-strand break repair. This step protects the 3’ overhanging DNA strand from degradation. After the transient RNA-DNA hybrid intermediate is formed the RNA strand is replaced by the RAD51 protein which then catalyzes the ssDNA invasion step of homologous recombination.

References

{{Polymerases Gene expression Proteins