FAQ: Is it possible to digest RNase R (NEB #M0100)-resistant linear RNAs?

Yes, we have tested two methods to digest RNase R-resistant linear RNAs. (1) NEB RNase R can be combined with NEB XRN-1 (NEB #M0338) and NEB RppH (NEB #M0356) in a one-pot reaction with 1X RNase R Reaction Buffer to maximize linear RNA removal. (2) Another method is to pre-treat RNA samples with NEB E. coli Poly(A) Polymerase (NEB #M0276) to lengthen the 3´ ends of the RNAs, which can improve RNase R binding and activity. The RNA needs to be cleaned up before proceeding with the RNase R reaction.