RNA Polymerases

Introduction

RNA polymerases are enzymes that catalyze the synthesis of RNA from DNA templates in a process called transcription. In all living organisms, there are three main types of RNA polymerases, designated as RNA polymerase I, II, and III (Pol I, Pol II, and Pol III), each with specific functions and properties.

Pol I is responsible for transcribing ribosomal RNA (rRNA) genes, which are used to build ribosomes, the cellular machinery responsible for protein synthesis. Pol I is a large enzyme that synthesizes a single precursor rRNA molecule, which is then processed to produce the mature 18S, 5.8S, and 28S rRNAs found in eukaryotes.

Overview

1. Synthesis of 5S ribosomal RNA
2. Synthesis of large ribosomal RNA
3. Synthesis of small nucleolar RNA
4. Synthesis of small ribosomal RNA
5. Synthesis of transfer RNA

Eukaryotic Overview

• 3 types of RNA polymerase
  • RNAp 1
    • synthesizes rRNA in nucleolus
    • remember: rRNA is most abundant RNA; so it is #1
  • RNAp 2
    • synthesizes mRNA, snRNA in nucleusa[href=”#rna-polymerases-q1″]#rna-polymerases-q1 
  • RNAp 3
    • synthesizes tRNA in nucleus
    • remember: tee = three
    • makes eukaryotic 5s rRNA
• Structure
  • similar in structure to prokaryotes
• Initiation
  • TFIID = initiation factor
  • binds RNAp to DNA
• Termination
  • translation continues far past gene and RNAp eventually falls off
• Clinical importance
  • inhibited by
    • α-amanitin
      • poison in death cap mushrooms
      • inhibits RNA polymerase 2 from synthesizing small nucleolar RNA and messenger RNA
      • leads to acute liver and kidney failure
    • actinomycin D

chemotherapeutic

Stages of RNA Polymerases

The RNA polymerase enzymes, Pol I, Pol II, and Pol III, all undergo a similar series of stages during the transcription process. These stages can be divided into three main steps: initiation, elongation, and termination.

1. Initiation: During initiation, the RNA polymerase binds to the DNA template at the promoter region of the gene to be transcribed. The binding of the RNA polymerase to the promoter is mediated by transcription factors and other regulatory proteins. The RNA polymerase then undergoes a series of conformational changes to form an open complex, in which the DNA strands are separated, and the template strand is exposed for base pairing with the incoming ribonucleoside triphosphate (rNTP).
2. Elongation: During elongation, the RNA polymerase synthesizes the RNA transcript by adding rNTPs to the growing RNA chain in a 5′ to 3′ direction. The RNA polymerase moves along the DNA template, unwinding the DNA ahead of it and rewinding it behind it. The elongation rate of the RNA polymerase is influenced by a variety of factors, including the sequence of the DNA template, the presence of DNA-binding proteins, and the local chromatin structure.
3. Termination: During termination, the RNA polymerase reaches the end of the gene and dissociates from the DNA template. In prokaryotes, termination is often mediated by the formation of a hairpin loop in the RNA transcript, which causes the RNA polymerase to pause and dissociate from the template. In eukaryotes, termination is more complex and involves the recognition of specific RNA sequences, as well as the action of termination factors and chromatin remodeling enzymes.

Overall, the transcription process is highly regulated and requires the coordinated action of many different proteins and regulatory elements to ensure the accurate and efficient synthesis of RNA from DNA templates. The study of RNA polymerase function and regulation is an important area of molecular biology and has significant implications for understanding gene expression and regulation.

Types of RNA polymerase

There are three main types of RNA polymerase in cells: RNA polymerase I, RNA polymerase II, and RNA polymerase III. Each type of RNA polymerase has a distinct function and synthesizes a different type of RNA.

1. RNA polymerase I: RNA polymerase I transcribes ribosomal RNA (rRNA) genes to produce the precursor rRNA molecules that will form the structural and functional components of ribosomes. In eukaryotic cells, RNA polymerase I is located in the nucleolus and synthesizes a large precursor rRNA molecule that is processed to produce the mature 18S, 5.8S, and 28S rRNAs.
2. RNA polymerase II: RNA polymerase II transcribes protein-coding genes to produce messenger RNA (mRNA) molecules that will be translated into proteins. RNA polymerase II is the most extensively studied RNA polymerase and is responsible for the regulation of gene expression in response to various cellular signals. It is also involved in the synthesis of many non-coding RNAs, such as microRNAs and long non-coding RNAs.
3. RNA polymerase III: RNA polymerase III transcribes a variety of small RNA molecules, including transfer RNAs (tRNAs), 5S ribosomal RNA (5S rRNA), and some small non-coding RNAs involved in RNA processing and modification. RNA polymerase III is the smallest of the three RNA polymerases and is less extensively studied than RNA polymerase II.

The three types of RNA polymerases have different subunit compositions and are subject to different regulatory mechanisms. The study of RNA polymerases and their regulation is a critical area of molecular biology and has led to significant advances in our understanding of gene expression and regulation.

Complications

RNA polymerases are highly regulated enzymes, and any disruption in their function can lead to various complications and diseases. Some of the complications associated with RNA polymerases include:

1. Cancer: Dysregulation of RNA polymerase II activity is a common feature of many types of cancer. Abnormal expression or activity of transcription factors, co-regulators, and chromatin remodeling factors can lead to uncontrolled transcription of oncogenes or the silencing of tumor suppressor genes.
2. Neurodegenerative diseases: Abnormal RNA polymerase II activity and transcriptional dysregulation have been implicated in the development of several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In some cases, the accumulation of misfolded proteins can interfere with RNA polymerase II function and disrupt normal gene expression patterns.
3. Genetic disorders: Mutations in genes encoding RNA polymerase subunits or transcription factors can cause a variety of genetic disorders. For example, mutations in the POLR1C and POLR1D genes, which encode subunits of RNA polymerase I, have been linked to Treacher Collins syndrome, a rare congenital disorder characterized by craniofacial abnormalities.
4. Viral infections: Many viruses, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), and human papillomavirus (HPV), rely on host RNA polymerases for their replication and transcription. These viruses have evolved strategies to subvert or manipulate RNA polymerase activity to facilitate their replication and evade host immune responses.

Understanding the molecular mechanisms that govern RNA polymerase function and regulation is crucial for the development of new therapies to treat these and other diseases. Ongoing research in this area is aimed at identifying novel targets for drug development and developing new strategies for manipulating gene expression to treat a wide range of human diseases.

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