Tunable Protein Domains for Enhanced Post-transcriptional Gene Regulation in Human Cells

Stanford scientists in Lacramioara Bintu's lab have developed a high-throughput system to identify regulatory domains in human RNA-binding proteins, presenting a new set of tools that could greatly enhance control over gene regulation at the RNA level for therapeutic and synthetic biology applications.

The field of gene regulation has increasingly identified the crucial role of post-transcriptional regulation via RNA-binding proteins (RBPs). However, until recent advances in RNA targeting and editing technologies, it has been challenging to achieve precise control of gene regulation in human cells at the RNA level. Existing tools often lack compact protein domains that can regulate mRNA fate in a tunable manner. Moreover, most current synthetic RNA tools are constitutive binders, making it difficult to manage gene regulation appropriately.

Stanford researchers have created a high-throughput system to identify and catalog RNA regulatory domains in human RNA-binding proteins, a key element in gene expression. This technology facilitates the identification of hundreds of protein domains, which when fused to an RNA-binding domain, can lead to mRNA degradation and prevent translation. The advantage of this system is its tunability, allowing more precise control over mRNA and subsequent protein levels, something that competing technologies and previous methods do not currently offer.

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Stage of Development:
Proof of concept - in vitro