Huifen Cao, Claes Wahlestedt, Philipp Kapranov

The past decade has seen an explosion of interest in long noncoding RNAs (lncRNAs). However, despite the massive volume of scientific data implicating these transcripts in a plethora of molecular and cellular processes, a great deal of controversy surrounds these RNAs. One of the main reasons for this lies in the multiple unique features of lncRNAs which limit the available methods used to characterize them. Combined with their vast numbers and inadequate classification, comprehensive annotation of these transcripts becomes a daunting task. The solution to this complex challenge likely lies in deep understanding of the strengths and weaknesses of each computational and empirical approach, and integration of multiple strategies to reduce noise, authenticate the results, and classify lncRNAs. We review here both the advantages and caveats of strategies commonly used for functional characterization and annotation of lncRNAs in the context of emerging conceptual guidelines for their application.