RNA Polymerase

RNA Polymerases Classification

In eukaryotes, there are four forms of RNA polymerase (I-IV), which are classified on the basis of the type of RNA they produce. RNA polymerase I (Pol I) makes a pre-ribosomal RNA (pre-rRNA 45S), which makes up ~50% of the RNA produced in a cell; RNA polymerase II (Pol II), which makes precursors of mRNAs, most snRNA and microRNAs; RNA polymerase III (Pol III), which makes tRNAs and rRNA 5S, as well as other small RNAs found in the cell. RNA polymerase IV is an enzyme, which makes small interfering RNA (siRNA) in plants.

Both bacteria and archaea each have only one type of RNA polymerase that is structurally similar to eukaryotic RNA polymerases. However, viruses employ different types of DNA-directed RNA polymerases, as well as RNA-dependent RNA polymerases (RdRp).

Transcription and RNA Types

During transcription, DNA-directed RNA polymerases direct the synthesis of an RNA chain complementary to the DNA template, by binding to a promoter sequence and initiating separation of the DNA double helix. Complementary ribonucleotide purine bases, adenine and guanine, and pyrimidine bases cytosine and uracil, bind and form the RNA chain, until a termination signal is reached.

DNA-directed RNA polymerases catalyze the production of either coding messenger RNA (mRNA), which become proteins, or non-coding RNA, sometimes called "RNA genes". There are four types of non-coding RNA:

• transfer RNA (tRNA) - adds amino acids to polypeptide chains in the ribosomal site of protein synthesis during the translation step of protein synthesis
• ribosomal RNA (rRNA) - incorporated into the ribosome
• micro RNA (miRNA) - involved in regulating gene activity
• catalytic RNA (ribozyme) - an RNA molecule that has catalytic abilities

DNA-directed RNA polymerase activity is tightly controlled throughout the initiation, elongation and termination phases of transcription by diverse regulatory signals ranging from protein factors to small molecule inhibitors. Newly transcribed RNA strands undergo post-transcriptional processing before leaving the nucleus. In contrast to DNA-directed RNA polymerases, RNA-dependent RNA polymerases catalyzes the direct replication of RNA, which produces an identical copy of RNA from an RNA template.

Role of RNA Polymerase in Epigenetics

DNA-directed RNA polymerase activity is a crucial requirement for the realization of epigenetic modifications, since it reads and translates both genetic and epigenetic information. An example of this is during X chromosome inactivation in females, whereby the RNA 'Xist' binds to and spreads out along the entire length of one of the two X chromosomes, blocking the access of the RNA polymerase and other transcription machinery. This prevention of transcription is key in regulating expression of genes located on the X chromosome.

RNA-dependent RNA Polymerase Inhibitors as Antivirals

RNA-dependent RNA polymerase (RdRP) inhibitors, such as the nucleoside analogs Favipiravir (Cat.no. 7225) and Remdesivir (Cat. no. 7226), have been developed as antivirals. Remdesivir is a prodrug of an adenosine nucleotide analog, which was originally developed in the efforts against the ebola virus disease and marburg virus infections. Favipiravir, a prodrug of a guanosine nucleotide analog, also inhibits RNA-dependent RNA polymerases. The ability of these inhibitors to inhibit viral replication has resulted in their also being evaluated as a treatment for SARS-CoV-2 infection, the virus responsible for the COVID-19 pandemic.

RNA Polymerase Gene Data