Circular RNA virus

Researchers at Indian Institute of Science Education and Research (IISER), Bhopal recently identified a circular RNA virus (ciTRAN) and its role in HIV-1 virus replication.

[ref- MDPI]

About Circular RNA (circRNA):

• It is a type of single-stranded RNA which forms a covalently closed continuous loop, the 3′ and 5′ ends normally present in an RNA molecule are joined together.
• It regulates gene expression and is essential for biological processes, development, and fighting diseases.
• It is resistant to exonucleolytic degradation by RNAase R due to circular nature.
• Exonucleolytic degradation: A Calcium-dependent extracellular nuclease enzyme that degrades high-molecular-weight native DNA.

Applications:

• RNA sequencing and bioinformatics in various cell lines and across different species.
• As an oncogenic stimulus or tumour suppressor in cancer.
• It is enriched and stable in extracellular fluid, indicating its potential as a cancer biomarker.

Functional consequences of circRNA on HIV-1 replication:

• Direct RNA nanopore sequencing (circDR-Seq) was used to capture circRNAs from HIV-1–infected T cells (white blood cells) and identify ciTRAN, a circRNA that modulates HIV-1 transcription.
• HIV-1 viral protein R (VpR) is a multifunctional protein that plays specific roles in HIV-1 viral life cycle and affects anti-HIV functions of the immune cells.
• HIV-1 infection induces ciTRAN expression in a Vpr-dependent manner and ciTRAN interacts with serine/arginine-rich splicing factor 1 (SRSF1), a protein to repress HIV-1 transcription.
  • VpR is a gene required for viral replication in nondividing cells like macrophages and proliferating target CD4+ T cells.
• HIV-1 hijacks ciTRAN which is altered during the immunological signaling, inflammation, and viral infection.
  • This prevents the function of SRSF1 and promotes efficient viral transcription.
• An SRSF1-inspired mimic can inhibit viral transcription regardless of ciTRAN induction.
• Potential applications: Develop novel drugs and therapies to fight HIV-1 virus.
• It can overcome transmission bottlenecks in primate lentiviruses.
• Challenges: Lack of information on virus and less availability of Circular RNA makes it difficult to detect its native form and characterize it.

Ref: Source