RNA methyltransferases involved in 5' cap biosynthesis

Byszewska, Magdalena; Smietanski, Miroslaw; Purta, Elzbieta; Bujnicki, Janusz M

In many instances, m 7 G-capped RNAs are modified further, in particular by additional methylation steps at the cap0 guanosine or methylation of the first few transcribed nucleoside residues. For instance, the cap0 guanosine is modified by addition of 2 methyl groups at the N 2 position, yielding a trimethylguanosine (m 2,2,7 G or TMG) cap, in some small nuclear RNAs (snRNAs) and nucleolar RNAs (snoRNAs) required for pre-mRNA splicing (e.g., U1, U2, U4, and U5), pre-rRNA processing (U3 and U8), and telomere addition (telomerase RNA), as well as in several selenoprotein mRNAs. 6 In higher eukaryotes, the 5 0 ends of mRNA and snRNA are modified further by ribose 2 0 -O-methylation on the first and second transcribed nucleosides, yielding cap1 and cap2 modifications, respectively. 7 In humans, cap0 and cap1 methylations are found on all mRNA molecules, while about half of the capped and polyadenylated RNA molecules contain a 2 0 -O-methylated residue at the second transcribed position. 8 The U1, U2, U4, and U5 snRNAs are methylated at both the first 2 positions. 9 Cap1 and cap2 methylations in U2 snRNA are required for the formation of spliceosomal E-complex and, as a consequence, for efficient pre-mRNA splicing. 10 In some organisms, such as in Trypanosomes, as many as 4 first residues of the nascent transcript undergo ribose methylation, to generate the cap4 structure. 11 These additional methylation steps are often important for RNA processing, translation and stability, although their role has not been fully elucidated.