TRIM28 mediates primer binding site-targeted silencing of Lys1,2 tRNA-utilizing retroviruses in embryonic cells.
Murine leukemia viruses (MLVs) and related retroelements are potently restricted in embryonic cells by postintegration transcriptional silencing, likely to protect the germ line from insertional mutagenesis. This silencing is in large part attributable to the presence of a nuclear repression complex, which targets a sequence element of the proviral DNA, the repressor-binding site. The repressor-binding site closely overlaps the tRNA primer binding site, a highly conserved sequence essential for virus replication and defining the site of initiation of DNA synthesis during reverse transcription. We have recently demonstrated that the cellular corepressor TRIM28 is recruited to the proline tRNA primer-binding site used by many MLVs and is required to mediate this silencing. Here, we show that TRIM28 is also required for the restriction of retroviruses using a completely distinct tRNA for the priming of their DNA synthesis, namely Lys-1,2 tRNA. These results generalize the role of TRIM28 in retroviral restriction and suggest that this system has evolved to restrict multiple retroviruses.
Wolf
Daniel
D
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Hug
Kevin
K
Goff
Stephen P
SP
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000821:virology*; D020868:Gene Silencing; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology*; D012357:RNA, Transfer, Lys / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D000076183:Tripartite Motif-Containing Protein 28; D014779:Virus Replication
D004279:DNA, Viral; D009687:Nuclear Proteins; D012357:RNA, Transfer, Lys; D012097:Repressor Proteins; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28