Ribonuclease L

Protein RNASEL PDB 1wdy

Ribonuclease L (RNase L) is an enzyme that plays a critical role in the cellular antiviral defense mechanisms. It is part of the interferon system, which is activated in response to viral infections. RNase L is encoded by the RNASEL gene in humans.

Function

RNase L is involved in the degradation of RNA in the presence of 2-5A synthetase, an enzyme that is activated by interferon signaling. When a cell is infected by a virus, interferons are produced and induce the production of several proteins, including 2-5A synthetase. This enzyme synthesizes 2',5'-oligoadenylates (2-5A) which then bind to RNase L, activating it. Once activated, RNase L degrades both viral and cellular RNA, leading to an inhibition of viral replication and ultimately apoptosis (programmed cell death), thereby limiting the spread of the virus.

Structure

RNase L is a dimeric enzyme, meaning it consists of two subunits. Each subunit contains an anion binding site, a 2-5A binding domain, and an RNA binding domain. The activation of RNase L by 2-5A leads to a conformational change that allows the enzyme to dimerize and become catalytically active.

Genetics

The human RNASEL gene is located on chromosome 1q25. It is composed of several exons and introns. Mutations in the RNASEL gene have been associated with increased susceptibility to viral infections and a rare hereditary prostate cancer syndrome, highlighting the importance of RNase L in antiviral defense and cell growth regulation.

Clinical Significance

1. 1. 1. Prostate Cancer

Research has shown that mutations in the RNASEL gene can lead to a hereditary form of prostate cancer. These mutations reduce the activity of RNase L, leading to decreased viral RNA degradation and potentially allowing viral infections to contribute to the development of cancer.

1. 1. 1. Viral Infections

RNase L plays a significant role in the defense against viral infections. Its activity is crucial for the degradation of viral RNA, preventing the replication of viruses within the host cell. Impairments in RNase L function can lead to increased susceptibility to various viral infections.

Research Directions

Current research is focused on understanding the precise mechanisms of RNase L activation and its role in antiviral defense and cell regulation. There is also interest in developing therapeutic strategies that can modulate RNase L activity, potentially offering new treatments for viral infections and RNase L-related diseases.