Chapter 1 12 RNA POL III - In health To comprehend the consequences of mutations in RNA polymerase III (Pol III) subunits, it is essential to understand its function under physiological conditions. Pol III is one of three eukaryotic RNA polymerases that transcribe DNA into RNA, each with distinct transcriptional specializations. Pol I transcribes pre-rRNAs, which are processed into the 18S, 5.8S, and 28S ribosomal RNAs (rRNAs), essential components of ribosome assembly. Pol II transcribes protein-coding genes into mRNAs and produces several regulatory RNAs, including most microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). In contrast, Pol III transcribes small, highly abundant non-coding RNAs (ncRNAs), typically less than 350 nucleotides in length, that are essential for various cellular processes. Among Pol III-transcribed transcripts are nuclear transfer RNAs (tRNAs) and 5S rRNA, which are both integral components of translation (Hoagland et al., 1958; Rosset & Monier, 1963). Ribosome binding and translation regulation are also mediated by Pol III transcripts, specifically, 7SL, BC200, snaR and Alu (Bishop et al., 1970; Houck et al., 1979; Mrazek et al., 2007; Parrott & Mathews, 2007; Watson & Sutcliffe, 1987). Other essential Pol III products are 7SK RNA, U6 and U6atac which are involved in transcription regulation and splicing (Lerner & Steitz, 1979; Zieve & Penman, 1976). Furthermore, transcripts RPPH1 and RMRP are key to tRNA and ribosomal RNA processing, while Y RNA plays a role in RNA stability, replication and translation regulation (Bartkiewicz et al., 1989; Lerner et al., 1981; Reddy et al., 1981). Also vault ribonucleoprotein (RNP) regulation of autophagy is mediated by Pol III transcript, vault RNA (Kedersha & Rome, 1986). Finally, Pol III transcript nc886 is involved in immune signalling (Mrazek et al., 2007; Nandy et al., 2009; Zhou & Van Bortle, 2023). Figure 3: Overview of RNA polymerase III transcriptome. Reused from (Zhou & Van Bortle, 2023)
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