FET protein family

FET protein family refers to a group of RNA-binding proteins that are implicated in various cellular processes, including RNA processing and the regulation of gene expression. The family is named after the three most extensively studied members: FUS, EWS, and TAF15. These proteins share a similar structure, including an RNA recognition motif (RRM) and a zinc finger domain, which are essential for their interaction with RNA and other proteins. Mutations in the genes encoding these proteins have been linked to several human diseases, notably amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and certain types of cancer.

Structure and Function

The FET proteins are characterized by their ability to bind RNA through their RNA recognition motif and zinc finger domain. This binding is crucial for their involvement in RNA processing events, such as splicing, transport, and stabilization. Additionally, these proteins can interact with other proteins through their prion-like domain, which is implicated in the formation of dynamic nuclear bodies and stress granules, suggesting a role in the cellular stress response.

Pathology

Mutations and dysregulation of FET proteins have been associated with a range of diseases. In neurodegenerative diseases like ALS and FTLD, abnormal aggregation of FET proteins in neurons is a hallmark. These aggregates are thought to disrupt normal cellular functions, leading to cell death. In cancer, alterations in the expression levels or mutations of FET proteins can affect gene expression patterns, promoting oncogenesis. The exact mechanisms by which FET proteins contribute to these diseases are an active area of research, with the hope that understanding these processes will lead to new therapeutic strategies.

Research and Clinical Implications

The involvement of FET proteins in critical cellular processes and diseases has made them a focus of research. Studies aim to elucidate the precise mechanisms by which these proteins regulate RNA metabolism and how their dysfunction contributes to disease. In the context of cancer, research is also directed at exploring the potential of targeting FET proteins for therapeutic purposes. Given their role in neurodegenerative diseases, FET proteins are also considered potential targets for the development of treatments for ALS and FTLD.