RNA Discovery

By Dr. Ananya Mandal, MDReviewed by April Cashin-Garbutt, MA (Editor)

The discovery of RNA began with the discovery of nucleic acids by Friedrich Miescher in 1868 who called the material 'nuclein' since it was found in the nucleus.

The discovery of RNA may be described chronologically as follows;

Between 1890 and 1950

• RNA was found to be distinctly different from DNA. This was noted by its sensitivity towards alkaline caused by an additional OH-group on the ribose
• Nucleic acids were isolated from various organisms
• ATP and GTP were proposed to be the cell’s general energy source and building blocks for RNA
• Chemical analysis revealed that RNA shares three bases with DNA: adenine, cytosine and guanine. Uracil as a base unique to RNA was discovered in place of thymine in DNA.
• It was in 1939 that the role of RNA in protein synthesis was discovered.

Between 1951 and 1965

• During this time the RNA types that are useful in protein synthesis were identified. Messenger RNA (mRNA) as the carrier of genetic information, transfer RNA (tRNA) acting as the physical link between mRNA and protein, and ribosomal RNA (rRNA) present in ribosomes for protein synthesis were identified.
• RNA polymerase was identified and purified.
• Severo Ochoa won the 1959 Nobel Prize in Medicine after he discovered how RNA is synthesized.
• The sequence of the 77 nucleotides of yeast tRNA was found by Robert W. Holley in 1965. Holley won the 1968 Nobel Prize in Medicine for his research.
• This period also saw the discovery of the genetic code that three of the bases coded uniquely for an amino acid.
• RNA acting as genetic code in some viruses was identified.

Between 1966 and 1975

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• Transfer RNAs were sequenced and identified. The typical clover leaf shape of the tRNA was identified.
• X ray crystallography was used to know the shape of RNA
• In 1967 Carl Woese found the catalytic properties of RNA and speculated that the earliest forms of life relied on RNA both to carry genetic information and to catalyze biochemical reactions.
• This period saw the discovery of the Reverse transcriptase copying RNA into DNA. This was opposed to the central dogma that stated that RNA is made from DNA alone and not vice versa.

Between 1976 and 1985

• In 1976, Walter Fiers and his team determined the first complete nucleotide sequence of an RNA virus genome, that of bacteriophage MS2
• Splicing RNA was found. Introns were found to interrupt genes in their copying and the need to remove these by splicing was found.
• RNA as a biological catalyst was found. The RNase P was discovered. This led to the hypothesis of RNA as the genetic element of the “RNA world hypothesis”.
• Small RNA and protein complexes performing the splicing of the pre mRNA molecules were discovered.
• Spliceosomes as large RNA-protein complexes mediating nuclear pre-mRNA splicing were found

Between 1986 to 2000

• Editing and modifications of RNA in the cell was discovered.
• Maintenance of chromosomal ends using RNA templates in telomerases was discovered.
• Ribosomes were found to be the largest RNA enzyme

From 2000 to present

• Small RNA molecules that can regulate gene expression by post-transcriptional gene silencing were discovered
• Long non-coding RNA regulating gene expression was found. The first one was termed Xist. These were found to control epigenetic phenomena.
• Riboswitches were found that control gene expression
• Use of RNA intermediates by mobile DNA was found.

Further Reading

• All RNA Content
• mRNA Medicine: what’s next after the COVID-19 vaccine?
• What is RNA?
• RNA Structure
• Types of RNA: mRNA, rRNA and tRNA