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The mysterious power of RNA polymerase III: Why is it key to cell growth?
In eukaryotic cells, RNA polymerase III (often abbreviated to Pol III) is a key protein responsible for transcribing DNA into a variety of small RNAs, including 5S ribosomal RNA and transfer RNA (tRNA). These RNA molecules play an indispensable role in cell growth and maintaining basic physiological functions. These genes, transcribed by RNA polymerase III, are classified as "housekeeping" genes, meaning that their expression is essential in all cell types and under most environmental conditions.
Therefore, the regulation of RNA polymerase III is directly related to the quality of cell growth and cycle regulation and requires fewer regulatory proteins than RNA polymerase II.
Under stress or adverse conditions, the activity of RNA polymerase III is inhibited. Maf1 protein is an important inhibitory factor, and rapamycin inhibits the activity of RNA polymerase III by directly acting on the TOR pathway.
The transcription process is a complex mechanism involving three major stages, including initiation, elongation, and termination. First, during the initiation phase, an RNA polymerase complex needs to be constructed on the promoter of the gene. This is followed by the elongation phase, during which RNA transcripts are synthesized, and finally the termination phase, during which the RNAP complex disassembles.
Startup Process
The initiation process of RNA polymerase III differs in some aspects from that of RNA polymerase II. Pol III generally relies on internal control sequences located within the transcribed region and does not require control sequences located upstream of the gene.
During the initiation of RNA polymerase III, transcription factors first bind to control sequences and then recruit TFIIIB (polymerase III transcription factor B) to form a complex.
The structure of TFIIIB is composed of three units, including TATA binding protein (TBP), TFIIB-associated factor (BRF1 or BRF2) and B double unit (BDP1). This overall architecture is quite similar to the structure of RNA polymerase II.
Extension process
During the elongation phase, TFIIIB remains bound to DNA after transcription initiation, allowing genes transcribed by Pol III to undergo high-frequency transcription reinitiation. Studies have shown that in the yeast Saccharomyces cerevisiae, the average speed of chain extension is 21 to 22 nucleotides per second, and the maximum speed can reach 29 nucleotides.
Terminate the process
As for the termination process, RNA polymerase III terminates transcription at a small poly-U sequence (5-6 uracils). In eukaryotes, although not essential, the presence of a hairpin loop can enhance termination efficiency in humans.
In yeast, studies have shown that transcription termination occurs stepwise at the sequence T7GT6 and suggest that insertion of a G nucleotide can reset the transcription rate.
Transcribed RNA
The main types of RNA that RNA polymerase III can transcribe include transfer RNA, 5S ribosomal RNA, U6 splicing RNA, etc. These RNAs play their own unique functions in various physiological processes within cells.
Role in DNA repairIn addition to its transcriptional function, RNA polymerase III also plays an important role in the homologous recombination repair process of DNA. It promotes the formation of temporary RNA-DNA hybrids upon DNA double-strand breaks, a critical intermediate step that helps protect the 3' overhanging DNA strand from degradation.
These actions of RNA polymerase III highlight its critical role in cell growth, metabolism, and maintaining genome stability. There are still many mysteries about its operation, and scientists are working hard to unravel these mysteries. In the future, as research on RNA polymerase III continues to deepen, perhaps we will have a clearer understanding of its importance in cellular life. Does this mean that RNA polymerase III will have more profound implications for future biomedicine?
