Srrt-KO Mouse

Srrt, also known as ARS2 (arsenite-resistance protein 2), is an essential eukaryotic protein. It is at the nexus of RNA polymerase II (Pol II) transcription, transcript maturation and quality control. Through interacting with the Cap Binding Complex (CBC), it associates with the cap of new RNAs, acting as a hub for protein factor exchanges that determine RNA fate. It is involved in maintaining the identity of various cell types, such as embryonic stem cells and neural stem cells, and may play a role in regulating the mitochondrial proteome [1,3,4,5].

In neural stem cells, selective knockdown of Ars2 (Srrt) in glial fibrillary acidic protein-expressing cells in the adult subventricular zone of mice depleted the number of neural stem cells and their neurogenic capacity. These phenotypes were recapitulated in hGFAP-cre::Ars2(fl/fl) conditional knockout mice, with more severe effects. Ex vivo assays showed that Ars2 was necessary and sufficient to promote neural stem cell self-renewal by positively regulating the expression of Sox2 [5]. In embryonic stem cells, Srrt sustains cell identity by preventing premature termination of numerous transcripts at cryptic cleavage/polyadenylation sites in first introns [4].

In conclusion, Srrt is crucial for maintaining cell identity in neural and embryonic stem cells through its roles in transcription and transcript processing. The gene knockout and conditional knockout mouse models have revealed its function in self-renewal and transcript regulation, which may have implications for understanding diseases related to stem cell function, such as certain neurological disorders and potentially cancer, given its association with prostate cancer progression [2,5].