Identification of RNA polymerase III-transcribed genes in eukaryotic genomes

The RNA polymerase (Pol) III transcription system is devoted to the production of short, generally abundant noncoding (nc) RNAs in all eukaryotic cells. Previously thought to be restricted to a few housekeeping genes easily detectable in genome sequences, the set of known Pol III-transcribed genes (class III genes) has been expanding in the last ten years, and the issue of their detection, annotation and actual expression has been stimulated and revived by the results of recent high-resolution genome-wide location analyses of the mammalian Pol III machinery, together with those of Pol III-centered computational studies and of ncRNA-focused transcriptomic approaches. In this article, we provide an outline of distinctive features of Pol III-transcribed genes that have allowed and currently allow for their detection in genome sequences, we critically review the currently practiced strategies for the identification of novel class III genes and transcripts, and we discuss emerging themes in Pol III transcription regulation which might orient future transcriptomic studies. This article is part of a Special Issue entitled: Transcription by Odd Pols.