Eukaryotic gene expression is dependent on the modification of the first 
transcribed nucleotide of pre-mRNA by the addition of the 7-methylguanosine cap. 
The cap protects transcripts from exonucleases and recruits complexes which 
mediate transcription elongation, processing and translation initiation. The cap 
is synthesized by a series of reactions which link 7-methylguanosine to the 
first transcribed nucleotide via a 5' to 5' triphosphate bridge. In mammals, cap 
synthesis is catalysed by the sequential action of RNGTT (RNA 
guanylyltransferase and 5'-phosphatase) and RNMT (RNA guanine-7 
methyltransferase), enzymes recruited to RNA pol II (polymerase II) during the 
early stages of transcription. We recently discovered that the mammalian cap 
methyltransferase is a heterodimer consisting of RNMT and the RNMT-activating 
subunit RAM (RNMT-activating mini-protein). RAM activates and stabilizes RNMT 
and thus is critical for cellular cap methylation and cell viability. In the 
present study we report that RNMT interacts with the N-terminal 45 amino acids 
of RAM, a domain necessary and sufficient for maximal RNMT activation. In 
contrast, smaller components of this RAM domain are sufficient to stabilize 
RNMT. RAM functions in the nucleus and we report that nuclear import of RAM is 
dependent on PY nuclear localization signals and Kapβ2 (karyopherin β2) nuclear 
transport protein.