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Unveiling the secrets of RNA polymerase III: How is transcriptional activity regulated under stress?
In eukaryotic cells, RNA polymerase III (Pol III for short) is a key protein responsible for transcribing DNA to synthesize 5S ribosomal RNA, transfer RNA (tRNA) and other small RNAs. These genes transcribed by Pol III are "day-to-day" genes, meaning that their expression is required for all cell types and most environmental conditions. Therefore, the regulation of Pol III transcription is mainly related to cell growth and cell cycle, and requires fewer regulatory proteins than RNA polymerase II. However, under stress conditions, Maf1 protein inhibits Pol III activity, while rapamycin inhibits Pol III activity by directly targeting TOR.
The transcription process is divided into three main stages: initiation, elongation, and termination.
Transcription process
Start
The initiation process of Pol III is special compared with Pol II, because it does not require regulatory sequences upstream of the gene, but usually relies on internal control sequences, that is, sequences located within the transcribed paragraph. Key factors in the initiation process include TFIIIB (polymerase III transcription factor B), which consists of three subunits: TATA-binding protein (TBP), a TFIIB-related factor (BRF1 or shallow period BRF2), and a B double-optimal unit ( BDP1).
TFIIIB plays a role in assembling Pol III during initiation, ensuring its correct positioning at the start site of transcription.
Class I, II and III
The initiation process of Pol III is usually divided into three categories, corresponding to the transcription of 5S rRNA, tRNA and U6 snRNA. During these processes, specific transcription factors first bind to control sequences and TFIIIB is subsequently recruited into the complex. Once TFIIIB binds, Pol III initiates RNA transcription.
Extension
In the transcription elongation phase of Pol III, TFIIIB remains bound to DNA after transcription is initiated, which results in a high restart rate for genes transcribed by Pol III. A study of yeast (Saccharomyces cerevisiae) showed that the average rate of chain elongation is about 21 to 22 nucleotides per second, with the fastest reaching 29 nucleotides. These data demonstrate the efficient performance of Pol III in RNA chain elongation.
Termination
Transcription by polymerase III is terminated after stretching of a small polyU. In eukaryotes, although the presence of a hairpin loop is not required, it may improve termination efficiency. Studies in yeast have found that transcription termination occurs at specific sequences. This finding highlights the influence of structural sequence properties on the termination process during transcription.
The types of RNA transcribed by RNA polymerase III include: transfer RNA, 5S ribosomal RNA, U6 spliceosome RNA, etc.
Function of RNA
RNA transcribed by RNA polymerase III displays numerous functions, including important roles in protein synthesis and gene regulation. These RNAs not only function based on their structure, but also participate in the transmission of some cell signals and are crucial to the physiological processes of cells.
Role in DNA repair
Recent studies have shown that RNA polymerase III also plays a crucial role in the DNA repair process, especially in the process of repairing DNA double-strand breaks by homologous recombination. Pol III's role includes promoting the formation of RNA-DNA hybrids, a process that is important for protecting DNA ends from degradation.
With a deeper understanding of the function of RNA polymerase III, we have discovered the complex role of this enzyme in cells coping with stress and maintaining genetic stability. As many unsolved mysteries are gradually revealed, this makes people think, will RNA polymerase III exert greater potential in future biomedical research?
