Recognition of the tRNA structure: Everything everywhere but not all at once

tRNAs are among the most abundant and essential biomolecules in cells. These spontaneously folding, extensively structured yet conformationally flexible anionic polymers literally bridge the worlds of RNAs and proteins, and serve as Rosetta stones that decipher and interpret the genetic code. Their ubiquitous presence, functional irreplaceability, and privileged access to cellular compartments and ribosomes render them prime targets for both endogenous regulation and exogenous manipulation. There is essentially no part of the tRNA that is not touched by another interaction partner, either as programmed or imposed by an external adversary. Recent progresses in genetic, biochemical, and structural analyses of the tRNA interactome produced a wealth of new knowledge into their interaction networks, regulatory functions, and molecular interfaces. In this review, I describe and illustrate the general principles of tRNA recognition by proteins and other RNAs, and discuss the underlying molecular mechanisms that deliver affinity, specificity, and functional competency.