Cmtr1, also called IFN-stimulated gene 95 kDa protein (ISG95), is an RNA cap methyltransferase. It methylates the first transcribed nucleotide of RNA polymerase II transcripts, creating part of the mammalian RNA cap structure. This methylation is involved in various gene-expression mechanisms, such as splicing, translation, and innate immune response evasion, and also plays a role in DNA replication and cell proliferation [2,3,4,5].

Loss-of-function studies have revealed its crucial roles. In colorectal cancer, knockdown of Cmtr1 significantly suppressed cell proliferation and tumorigenicity both in vitro and in vivo. Mechanistically, it inhibited RNAPII recruitment to the transcription start site of STAT3, suppressing STAT3 expression and activation. Additionally, Cmtr1 knockdown enhanced the efficacy of PD1 blockade immunotherapy via increased infiltration of CD8 + T cells into the tumor microenvironment [1]. In mouse models, loss of Cmtr1 leads to embryonic lethality, and conditional deletion in the germline causes infertility. Also, in Cmtr1 mutant adult mouse livers, there is chronic activation of the interferon pathway [6].

In conclusion, Cmtr1 is essential for various biological processes like embryonic development, fertility, and cell proliferation. Its role in diseases such as colorectal cancer has been highlighted through functional studies, especially those using gene-knockout models. These models have provided insights into its function in tumorigenesis and immune regulation, offering potential targets for therapeutic intervention.