Small RNA fragments derived from tRNA precursors have been observed since the 70s, but the depth of the small RNA degradome has only recently been observed with application of high-throughput RNA sequencing. Initially overlooked as degradation products, evidence of the stability and preferential processing patterns of small RNAs derived from tRNAs, snoRNAs and other constitutively expressed ncRNAs suggest functionality. Reminiscent of the size and processing patterns of microRNAs the potential of tRNA and snoRNA derived small RNAs to have regulatory function has been postulated. Indeed several regulatory RNAs derived from snoRNAs (small nucleolar RNAs), tRNAs (transfer RNAs) and vRNAs (vault RNAs) have been described. Using degradome-seq on a human breast cancer cell line we observe endonuclease processing of precursor ncRNAs on a wide scale, and using Argonaute HITS-CLIP (High through-put cross linking immunoprecipitation) and RNA-seq we observe defined small RNAs also on a large scale, many of which are bound to Argonaute. To test the hypothesised regulatory function we used reporter assays with target sites cloned downstream of a luciferase reporter. The vast majority of the ~40 RNA fragments tested showed an inability to repress its perfect target in comparison to known microRNAs which effectively repressed their target even when they are only moderately abundant, and the reporter was effectively suppressed when a microRNA mimic of identical sequence was transfected. This work expands our understanding of the existence and processing of small RNAs derived from ncRNA and but provides the much needed functional evidence to argue against the hypothesis that that they are regulatory RNAs.