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RNA World

Welcome to the RNA World Learning Project. This learning project allows Wikiversity participants to explore the so-called "RNA world hypothesis". The phrase RNA World is used in biology when exploring the idea that RNA molecules may have served as genetic molecules and enzymes before DNA and proteins.

Figure 1. Key polymerase activities of the RNA World and known organisms. Plants, fungi, protozoa, and certain animals use a cell-encoded RNA-dependent RNA polymerase (cRdRP) to amplify RNAs used for RNA Silencing.

The first specific genetic role discovered for RNA in cells was as mRNA intermediates between DNA genes and the proteins specified by genes. However, it also became evident that RNA can carry genetic instructions in RNA viruses such as Tobacco mosaic virus. Later it was realized that RNA molecules can function as enzymes, raising the prospect that life forms with only RNA but no DNA and protein might be possible.

RNA Silencing

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Figure 2. Molecular structure diagram of the QDE-1 RNA interference polymerase[1].

RNA silencing is a cellular phenomenon in which short, double-stranded RNA "triggers" can prevent the expression of specific genes[2]. RNA Silencing is also known as "RNA-mediated interference" (abbreviated RNAi). RNA interference is now recognized as a widespread, if not ubiquitous in eukaryotic organisms. The phenomenon of RNAi has caused great excitement as an experimental technique for selectively blocking gene expression with potential medical uses. The Nobel Prize in Physiology or Medicine in 2006 was awarded to Andrew Z. Fire and Craig C. Mello for their research on RNA interference [3]. (Wikiversity article about this Nobel Prize)

In some organisms the RNA molecules that target the RNA silencing process can be amplified. In plants, protozoa, fungi, and some animals such as nematode wormsthere is an enzyme called RNA-dependent RNA polymerase that generates base pair-complementary strands of RNA using an existing strand of RNA as a template. Such amplification of the RNA silencing process is important for protecting many eukaryotes from RNA viruses. Such a role for RNA interference was first found in plants, but has also been found in some animals[4].

Paula Salgado and her colleagues have studied the structure of one such polymerase, called QDE-1. The structure of QDE-1 is similar to the structure of DNA-dependent RNA polymerase. Paula Salgado et al suggested that a QDE-1-like polymerase may have been a very early protein polymerase, even pre-dating eukaryotic DNA-dependent RNA polymerase. If so, QDE-1 and RNAi might have their origins near the time of transition from the RNA World to the DNA-dominated world of cellular life.

When a gene is transcribed and translated to generate a protein, the process begins with a DNA-dependent RNA polymerase. Like QDE-1, DNA-dependent RNA polymerases generate strands of RNA—the difference is that they use a DNA template to do it. The RNA they generate is called messenger RNA and is in turn used as the template for building a protein out of amino acids. The structures of DNA-dependent RNA polymerases have been described previously, so Salgado et al could compare them with their new structure of QDE-1.

What they found was a remarkable similarity (Figure 3, below). Both DNA-dependent RNA polymerases and QDE-1 have an active catalytic site—the working core of the enzyme—that is formed by two distinctive structural domains called double-psi β-barrels. This strong structural resemblance between QDE-1 and the DNA-dependent RNA polymerases points towards an evolutionary link between the two types of RNA polymerase.

An influential theory on the origin of life proposes that RNA molecules were the first self-replicating molecules, forming a kind of precellular life in an "RNA world" (Figure 1, above). Initially, RNA molecules would have had to act as enzymes as well as genetic information so that they could replicate, but it is likely that an RNA-dependent RNA polymerase would have been one of the earliest protein-based enzymes to evolve.

 
Figure 3. Structural comparison of the RNA-dependent RNA polymerase (cRdRP) involved in the amplification of RNAi signals compared to the structure of a DNA-dependent RNA polymerase. Structurally equivalent regions are shown in dark colors, non-equivalent parts of the structures are shown in light colors[5].


Activities

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This section provides activities for further study.

Your questions

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List any questions you have about the RNA World hypothesis:

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nature of dna and rna

Discussions

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Read The Structure of an RNAi Polymerase Links RNA Silencing and Transcription by Paula S Salgado, et al. Discuss the implications of their results for the idea that the mechanisms of RNA-mediated gene expression silencing can suggest features of the ancient RNA-based proto-metabolism of Earth.

References

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  1. ↑ This figure is from: RNA Silencing Sheds Light on the RNA World by Rachel Jones in PLoS Biology 4(12): e448.
  2. ↑ This section is modified from: RNA Silencing Sheds Light on the RNA World by Rachel Jones in PLoS Biology 4(12): e448.
  3. ↑ 2006 award at the Nobel Prize website.
  4. ↑ Antiviral silencing in animals by Hong-Wei Li and Shou-Wei Ding in FEBS Lett. (2005) Volume 579, pages 5965–5973.
  5. ↑ The Structure of an RNAi Polymerase Links RNA Silencing and Transcription by Paula S. Salgado, Minni R. L. Koivunen, Eugene V. Makeyev, Dennis H. Bamford, David I. Stuart and Jonathan M. Grimes in PLoS Biology Volume 4, No. 12, e434.

Other Sources

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