Genome-wide mapping of infection-induced SINE RNAs reveals a role in selective mRNA export

Nucleic Acids Res. 2017 Jun 2;45(10):6194-6208. doi: 10.1093/nar/gkx180.

Abstract

Short interspersed nuclear elements (SINEs) are retrotransposons evolutionarily derived from endogenous RNA Polymerase III RNAs. Though SINE elements have undergone exaptation into gene regulatory elements, how transcribed SINE RNA impacts transcriptional and post-transcriptional regulation is largely unknown. This is partly due to a lack of information regarding which of the loci have transcriptional potential. Here, we present an approach (short interspersed nuclear element sequencing, SINE-seq), which selectively profiles RNA Polymerase III-derived SINE RNA, thereby identifying transcriptionally active SINE loci. Applying SINE-seq to monitor murine B2 SINE expression during a gammaherpesvirus infection revealed transcription from 28 270 SINE loci, with ∼50% of active SINE elements residing within annotated RNA Polymerase II loci. Furthermore, B2 RNA can form intermolecular RNA-RNA interactions with complementary mRNAs, leading to nuclear retention of the targeted mRNA via a mechanism involving p54nrb. These findings illuminate a pathway for the selective regulation of mRNA export during stress via retrotransposon activation.

MeSH terms

  • Animals
  • Biological Transport / genetics
  • Cell Cycle Proteins / genetics
  • Gene Expression Regulation / genetics*
  • Gene Knockdown Techniques
  • Herpesviridae Infections / genetics
  • Mice
  • NIH 3T3 Cells
  • Nuclear Matrix-Associated Proteins / metabolism
  • RNA Interference
  • RNA Polymerase III / genetics
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism
  • Retroelements / physiology
  • Rhadinovirus
  • Sequence Analysis, DNA
  • Short Interspersed Nucleotide Elements / genetics*
  • Stress, Physiological / genetics
  • Subcellular Fractions / metabolism
  • Transcription, Genetic
  • Tumor Virus Infections / genetics

Substances

  • Cell Cycle Proteins
  • Nuclear Matrix-Associated Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • Retroelements
  • SGOL2 protein, mouse
  • p54nrb protein, mouse
  • RNA Polymerase III