High throughput RNA sequencing has accelerated discovery of the regulatory roles of many small RNAs, but RNAs containing "hard stop" modifications have largely escaped detection due to interference with reverse transcription during RNA-seq library preparation.I will describe new methods that enable transcriptome-scale mapping of highly modified RNAs, as well as an efficient method to identify and monitor changes in the abundance or modification state of any small RNA with these modifications.Using these methods, we are finally able to begin unraveling the complex regulatory programs of hundreds of unique human tRNAs, as well as to explore the large number of mostly overlooked tRNA-derived RNAs, some of which have already been linked to control of global translation rates, cancer cell proliferation, apoptosis, and core metabolic pathways.