Whole-genome expression analysis of mammalian-wide interspersed repeat elements in human cell lines

摘要

With more than 500,000 copies, mammalian-wide interspersed repeats (MIRs), a sub-group of SINEs, represent similar to 2.5% of the human genome and one of the most numerous family of potential targets for the RNA polymerase (Pol) III transcription machinery. Since MIR elements ceased to amplify similar to 130 myr ago, previous studies primarily focused on their genomic impact, while the issue of their expression has not been extensively addressed. We applied a dedicated bioinformatic pipeline to ENCODE RNA-Seq datasets of seven human cell lines and, for the first time, we were able to define the Pol III-driven MIR transcriptome at single-locus resolution. While the majority of Pol III-transcribed MIR elements are cell-specific, we discovered a small set of ubiquitously transcribed MIRs mapping within Pol II-transcribed genes in antisense orientation that could influence the expression of the overlapping gene. We also identified novel Pol III-transcribed ncRNAs, deriving from transcription of annotated MIR fragments flanked by unique MIR-unrelated sequences, and confirmed the role of Pol III-specific internal promoter elements in MIR transcription. Besides demonstrating widespread transcription at these retrotranspositionally inactive elements in human cells, the ability to profile MIR expression at single-locus resolution will facilitate their study in different cell types and states including pathological alterations.