Journal
SCIENCE ADVANCES
Volume 9, Issue 36, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.adh9170
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HIV-1 infection induces the expression of ciTRAN, which interacts with SRSF1 to promote viral transcription. Additionally, an SRSF1-inspired mimic can inhibit viral transcription.
The functional consequences of circular RNA (circRNA) expression on HIV-1 replication are largely unknown. Using a customized protocol involving direct RNA nanopore sequencing, here, we captured circRNAs from HIV-1-infected T cells and identified ciTRAN, a circRNA that modulates HIV-1 transcription. We found that HIV-1 infection induces ciTRAN expression in a Vpr-dependent manner and that ciTRAN interacts with SRSF1, a protein known to repress HIV-1 transcription. Our results suggest that HIV-1 hijacks ciTRAN to exclude serine/ arginine-rich splicing factor 1 (SRSF1) from the viral transcriptional complex, thereby promoting efficient viral transcription. In addition, we demonstrate that an SRSF1-inspired mimic can inhibit viral transcription regardless of ciTRAN induction. The hijacking of a host circRNA thus represents a previously unknown facet of primate lentiviruses in overcoming transmission bottlenecks.
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