The RNA extension results with 1f as the template indicated that m 1 A has a dramatic effect on the activity of SC2RC. The reaction was largely stopped with only a tiny portion of the primer being able to be extended beyond the modified nucleotide. It is possible that m 1 A completely stopped the reaction and the tiny amount of 1h was a result of the conversion of m 1 A to m 6 A via the Dimroth rearrangement during the RNA extension reaction. However, RP HPLC analysis of 1f by comparing with 1e indicated that the isomerization is not easy. Storing the solution of 1f at -20 o C over one month did not result in any rearrangement (supporting information). To find out if the isomerization was easier to occur under the RNA extension reaction conditions, we subjected 1f to the otherwise identical RNA extension conditions except that SC2RC and 1a were not added. The mixture was then analyzed with RP HPLC. The profile was compared with those generated from the mixture of 1f, which contained m 1 A, and 1e, which had the same sequence of 1f but with m 1 A being m 6 A. Although it was hard to determine if isomerization occurred or not, according to the data, we tended to believe that a tiny portion of 1f was isomerized to 1e (supporting information). Therefore, we are more inclined to conclude that m 1 A completely blocked the RNA extension reaction and the tiny amount of 1h was a result of Dimroth rearrangement.