RNA methyltransferases involved in 5' cap biosynthesis

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

The g-methylphosphate cap structure is unique in that it is an alternative to the guanosine-containing cap. It is formed by a single methyltransfer reaction to a g -phosphate oxygen at the 5 0 end of the primary transcripts of certain small RNA molecules such as mammalian U6 and 7SK, mouse B2 and plant U3. 74 The enzyme responsible for this reaction, Bicoid-interacting protein 3 (Bin3), is a methyltransferase conserved in eukaryotes. It is, however, absent from S. cerevisiae. 75, 76 A structure of the human Bin3 homolog (BCDIN3) was determined, revealing a conserved RFM core (Fig. 5 ). An enzyme-substrate complex is not yet available, and the details of protein-RNA recognition and the mechanism of discrimination between Bin3 substrates and non-substrates remain to be determined. Trimethylguanosine synthase catalyzes hypermethylation of cap0 structure. In a 2step reaction, 2 methyl groups are transferred to the amine group of m 7 G and, as a result, the m 2,2,7 G structure is formed. The crystal structure of human TGS1 methyltransferase in complex with m 7 Gppp and SAH (shown in stick representation) is deposited in the PDB as 3GDH. Secondary structure elements that correspond to elements of the conserved RFM core are labeled. Secondary structure elements outside of the conserved core are not labeled.