History of RNA

History of RNA

1890 — 1950

›RNA is different‹

↗ RNA distinguishes itself from DNA by its sensitivity towards alkaline caused by an additional OH-group on the ribose.

↗ Detailed chemical analyses revealed that RNA shares three bases with DNA: adenine, cytosine and guanine. In contrast, uracil is unique to RNA whereas thymine is generally present in DNA.

↗ Nucleic acids were isolated from various organisms.

↗ The RNA building blocks ATP and GTP were proposed to be the cell’s general energy source: life’s engine.

1951 — 1965

›RNA makes proteins‹

↗ Three different species of RNA were identified as translating the genetic information (DNA) into proteins:
• 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, the protein factories.

↗ The genetic code was solved: three bases encode one amino acid.

↗ RNA polymerase, the enzyme synthesizing RNA from a DNA template, was purified.

↗ RNA acts as genetic information in viruses.

1966 — 1975

›The first RNA-SEQ‹

↗ Transfer RNA (tRNA) was analyzed:
• tRNAs were sequenced as the first long RNAs.
• The secondary structure of tRNA was predicted by evolutionary comparisons (“tRNA cloverleaf”).
• The tRNA 3d structure was solved by X-ray crystallography (L-shape).

↗ mRNAs were isolated and the addition of non-encoded nucleotides to RNAs (cap, polyA, CCA) was determined.

↗ Reverse transcriptase copying RNA into DNA was characterized.
This weakened the central dogma: DNA makes RNA makes protein.

1976 — 1980

›Splicing of RNA‹

↗ Introns interrupt genes and have to be removed from RNA transcripts by splicing.

↗ Small RNA-protein complexes are highly abundant in the nucleus and they are essential for pre-mRNA splicing.

↗ The comparison of ribosomal RNA sequences of many organisms provide insight into the evolutionary history of all kingdoms.

1981 — 1985

›RNA as an enzyme‹

↗ RNA by itself is catalytically active: group I, group II introns, RNase P, and hammerhead.

↗ RNA as mobile genetic elements: excised introns can reinsert into the genome.

↗ Spliceosomes are large RNA-protein complexes mediating nuclear pre-mRNA splicing.

↗ Alternative pre-mRNA splicing generates multiple proteins from a single gene.

↗ RNA as a catalytic enzyme and as a genetic element led to the “RNA world hypothesis.”

1986 — 2000

›RNA editing and in vitro evolution‹

↗ RNAs can be edited and modified in many different ways within cells.

↗ In vitro selection of RNA molecules (SELEX) allows for the evolution of functional RNA in the test tube.

↗ Chromosome ends are maintained using RNA templates in telomerases.

↗ Ribosomes as the largest RNA enzyme: RNA catalyzes peptide bond formation.

2000 — present

›Regulatory RNAs‹

↗ Small RNA molecules regulate gene expression by post-transcriptional gene silencing.

↗ Xist: the first long non-coding RNA regulating gene expression.

↗ Non-coding RNAs control epigenetic phenomena.

↗ Transcriptomics: most of the genome is transcribed at some point in time and space.

↗ Riboswitches bind cellular metabolites and control gene expression.

↗ Many mobile DNA elements use an RNA intermediate.