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The great mission of small RNAs: How does RNA polymerase III support DNA repair?
In eukaryotic cells, RNA polymerase III (Pol III for short) is a key protein responsible for transcribing DNA into 5S ribosomal RNA, transfer RNA (tRNA) and other small RNAs. These genes, transcribed by RNA polymerase III, belong to the category of "basic genes" whose expression is required in all cell types and under most environmental conditions. Therefore, the regulation of Pol III transcription is mainly related to the regulation of cell growth and cell cycle, and therefore requires fewer regulatory proteins than RNA polymerase II. However, under stress conditions, the Maf1 protein inhibits Pol III activity, and rapamycin inhibits Pol III function by directly targeting TOR.
Transcription process
The transcription process (regardless of which polymerase is performed) is divided into three main stages:
- Startup: RNA polymerase complex needs to be constructed on the promoter of the gene
- Elongation: Synthesis of RNA Transcription
- Termination: Complete RNA transcription and disassemble the RNA polymerase complex
Startup process
Compared with Pol II, Pol III is characterized by the fact that it does not require control sequences upstream of the gene and usually relies on internal control sequences, that is, sequences in the transcribed region. Pol III initiation is divided into three categories, corresponding to the initiation of 5S rRNA, tRNA, and U6 snRNA.
"TFIIIB is composed of three subunits: TATA binding protein (TBP), TFIIB-related factor (BRF1 or BRF2) and B-double protein (BDP1)."
Class I: Initiation of 5S rRNA
During the initiation of the 5S rRNA (category I) gene, TFIIIA first binds to the C region of the 5S rRNA control sequence located in the transcribed DNA sequence, and then TFIIIC introduces TFIIIB and assembles Pol III.
Class II: Initiation of tRNA
For tRNA (category II) initiation, TFIIIC binds to control sequence A and B regions and positions TFIIIB to bind DNA at the transcription start site.
Class III: Initiation of U6 snRNA
In the initiation of U6 snRNA (category III), SNAPc will bind to sequences upstream of the initiation site, a process that is enhanced by the Pol II transcription factor and ultimately promotes the assembly of TFIIIB.
Extension process
TFIIIB continues to bind to DNA after Pol III initiates transcription, unlike most basic transcription factors for Pol II transcription, which results in a high restart rate of Pol III transcribed genes.
"A study in the yeast Saccharomyces cerevisiae found that the average rate at which RNA chains extend is 21 to 22 nucleotides per second."
Termination process
Pol III terminates transcription on small polyureas (5 to 6 U), and although the hairpin structure is not required in eukaryotes, its presence may increase termination efficiency.
Transcribed small RNA
RNA transcribed by RNA polymerase III includes:
- Transfer RNA (tRNA)
- 5S ribosomal RNA
- U6 spliceosomal RNA
- RNase P and RNase MRP RNA
- 7SL RNA (RNA component of signal recognition particles)
- Various microRNAs
- Small nucleolar RNA
- Several gene regulatory antisense RNAs
Role in DNA repair
RNA polymerase III appears to be critical for repair of DNA double-strand breaks by homologous recombination. It promotes the formation of transient RNA-DNA hybrids at double-strand breaks, an essential intermediate step in homologous recombination-mediated double-strand break repair.
"This step protects the 3' end of the DNA strand from degradation, and the RNA strand is subsequently replaced by the RAD51 protein."
In an ever-changing biological environment, RNA polymerase III maps out how to protect cellular processes and plays an indispensable role in cooperating with DNA repair. Have you ever thought about the importance of the tasks of these small RNAs in cells to overall genome stability?
