 Robert Silber

Robert Silber is a researcher credited with early characterization of RNA ligases. His full name and New York University medicine affiliation appear on the original 1972 article, although the indexed citation abbreviates the byline as R. Silber.^[ref]

Silber and collaborators investigated an RNA ligase from phage-infected Escherichia coli. The purified enzyme converted labelled terminal phosphate groups into internal phosphodiester bonds, requiring ATP and magnesium. Resistance to alkaline phosphatase, together with tests using exonucleases, supported joining the two ends of an individual RNA chain to produce circular RNA under the studied conditions.^[ref]

The experiment illustrates why several chemical observations are needed to establish molecular topology. A label no longer accessible at a chain end suggests a change in its chemical setting, but that result alone does not determine whether two different molecules joined or one molecule closed on itself.

An original counting model makes the ambiguity precise. Begin with $100$ linear chains, each with two free ends, giving $200$ ends. Closing $40$ chains into separate rings leaves $60$ linear chains, $120$ free ends and $100$ total molecules. Alternatively, joining $40$ disjoint pairs into longer linear chains leaves $60$ molecules, again with $120$ free ends. The same reduction in end count can therefore accompany different molecular products. These are invented counts, not the paper's measurements; additional chemical and size information is needed to distinguish the products.

The historical inference combined the protected label with evidence that the product lacked accessible opposite ends. It was an inference about the tested RNA substrate and assay, not a claim that every RNA ligase reaction always creates a circle.^[ref]