Cap-specific adenosine methyltransferase (PCIF1) (PCIF1)

Cap-specific adenosine methyltransferase (PCIF1) is an enzyme responsible for catalyzing the methylation of the adenosine nucleotide at the transcription start site of eukaryotic mRNAs, generating the N(6),2'-O-dimethyladenosine (m6Am) RNA cap structure[3][2]. It is recruited to active RNA polymerase II via specific interactions and co-transcriptionally installs the m6Am mark, affecting mRNA stability, translation, and regulation of gene expression[2][3]. PCIF1 has emerging roles in cancer biology as it stabilizes certain oncogenic transcripts (notably FOS) and contributes to tumor growth and resistance to immunotherapy, especially anti-PD-1 in colorectal cancer models[1]. PCIF1 also modifies viral mRNA caps, facilitating viral evasion of innate immune responses by dampening type I interferon effects[4]. Genetic knockout in animal models is generally tolerated but alters gene expression in a tissue-dependent manner[2]. No registered drugs specifically target PCIF1, but experimental strategies include gene silencing by RNA interference in cancer. PCIF1 is also known by several aliases, including CAPAM, C20orf67, PPP1R121, MT-A70, and others.

Other names

mRNA (2'-O-methyladenosine-N(6)-)-methyltransferaseCAPAMC20orf67PPP1R121hCAPAMhPCIF1bA465L10.1MT-A70Cap-specific adenosine methyltransferaseProtein phosphatase 1 regulatory subunit 121PDX-1 C terminus-interacting factor 1PDX1 C-terminal inhibiting factor 1

For experimental RNA-targeting drugs: Silencing or inhibition of PCIF1 reduces m6Am cap methylation, destabilizes oncogenic transcripts (such as FOS), suppresses tumor growth, and enhances sensitivity to immunotherapy (anti-PD-1)[1]. Proposed: Targeting PCIF1 inhibits cancer cell proliferation, invasion, and adhesion, affecting TGF-β and interferon signaling[1][4].