The transcriptional transactivator Tat selectively regulates viral splicing.
HIV-1 gene expression requires both viral and cellular factors to control and coordinate transcription. While the viral factor Tat is known for its transcriptional transactivator properties, we present evidence for an unexpected function of Tat in viral splicing regulation. We used a series of HIV-1 reporter minigenes to demonstrate that Tat's role in splicing is dependent on the cellular co-transcriptional splicing activators Tat-SF1 and CA150. Surprisingly, we show that this Tat-mediated splicing function is independent from transcriptional activation. In the context of the full-length viral genome, this mechanism promotes an autoregulatory feedback that decreases expression of tat and favors expression of the env-specific mRNA. Our data demonstrate that Tat-mediated regulation of transcription and splicing can be uncoupled and suggest a mechanism for the involvement of specific transcriptional activators in splicing.
Jablonski
Joseph A
JA
Basic Science Department, Florida Atlantic University, Boca Raton, FL 33431, USA.
Amelio
Antonio L
AL
Giacca
Mauro
M
Caputi
Massimo
M
D017398:Alternative Splicing; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D012319:RNA Polymerase II / Q000378:metabolism; D022821:RNA Splice Sites; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation; D035602:Transcriptional Elongation Factors; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
C101819:HTATSF1 protein, human; D022821:RNA Splice Sites; C108440:TCERG1 protein, human; D015534:Trans-Activators; D035602:Transcriptional Elongation Factors; D054299:env Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1; D054322:tat Gene Products, Human Immunodeficiency Virus; D012319:RNA Polymerase II