Genome-wide mapping of infection-induced SINE RNAs reveals a role in selective mRNA export.
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.
Howard Hughes Medical Institute, University of California, Berkeley, CA 94720-3370, USA.|Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720-3370, USA.|Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232-2363, USA.
John
J
Karijolich
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232-2363, USA.
Yang
Y
Zhao
California Institute for Quantitative Biology, University of California, Berkeley, CA 94720-3370, USA.
Ravi
R
Alla
Howard Hughes Medical Institute, University of California, Berkeley, CA 94720-3370, USA.|Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720-3370, USA.|California Institute for Quantitative Biology, University of California, Berkeley, CA 94720-3370, USA.
Britt
B
Glaunsinger
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006566:Herpesviridae Infections / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D034622:RNA Interference; D012320:RNA Polymerase III / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D018626:Retroelements / Q000502:physiology; D018144:Rhadinovirus; D017422:Sequence Analysis, DNA; D020086:Short Interspersed Nucleotide Elements / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics; D013347:Subcellular Fractions / Q000378:metabolism; D014158:Transcription, Genetic; D014412:Tumor Virus Infections / Q000235:genetics; D004268:DNA-Binding Proteins
D018797:Cell Cycle Proteins; D034521:Nuclear Matrix-Associated Proteins; D012320:RNA Polymerase III; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018626:Retroelements; C532340:SGOL2 protein, mouse; C500331:Nono protein, mouse; D004268:DNA-Binding Proteins