text: The earliest work in RNA structural biology coincided, more or less, with the work being done on DNA in the early 1950s.  In their seminal 1953 paper, Watson and Crick suggested that van der Waals crowding by the 2`OH group of ribose would preclude RNA from adopting a double helical structure identical to the model they proposed—what we now know as B-form DNA. This provoked questions about the three-dimensional structure of RNA: could this molecule form some type of helical structure, and if so, how?  As with DNA, early structural work on RNA centered around isolation of native RNA polymers for fiber diffraction analysis.  In part because of heterogeneity of the samples tested, early fiber diffraction patterns were usually ambiguous and not readily interpretable.  In 1955, Marianne Grunberg-Manago and colleagues published a paper describing the enzyme polynucleotide phosphorylase, which cleaved a phosphate group from nucleotide diphosphates to catalyze their polymerization. This discovery allowed researchers to synthesize homogenous nucleotide polymers, which they then combined to produce double stranded molecules.  These samples yielded the most readily interpretable fiber diffraction patterns yet obtained, suggesting an ordered, helical structure for cognate, double stranded RNA that differed from that observed in DNA.  These results paved the way for a series of investigations into the various properties and propensities of RNA.  Through the late 1950s and early 1960s, numerous papers were published on various topics in RNA structure, including RNA-DNA hybridization, triple stranded RNA, and even small-scale crystallography of RNA di-nucleotides—G-C, and A-U—in primitive helix-like arrangements. For a more in-depth review of the early work in RNA structural biology, see the article The Era of RNA Awakening: Structural biology of RNA in the early years by Alexander Rich.