Recently, a new technique, combining Methylated RNA Immunoprecipatation with RNA sequencing (MeRIP-Seq), was developed and applied to survey the global mRNA N6-methyladenosine (m6A) methylation in mammalian cells. MeRIP-Seq has the potential to survey, for the first time, the transcriptome-wide distribution of different types of post-transcriptional RNA modifications. Yet, this new technology poses unique bioinformatics problems that call for novel and sophisticated statistical computational solutions. Here, we propose a novel computational framework that extends the features of exomePeak, our previously developed MeRIP-Seq analysis software package, to enable differential analysis by comparing the RNA epigenome from two different experimental conditions. Different from current available software packages developed for DNA epigenetics differential analysis that monitor the changes in the absolute amount of modified molecules, such as DESeq or edgeR, which may result from transcriptional differential expression in MeRIP-Seq, it monitors the percentage of modified RNA molecules which directly reflects the strength of post-transcriptional RNA modification. To demonstrate the utility of the software package, it was evaluated on a MeRIP-Seq data from HepG2 cell line. The new ExomePeak detected more than 16000 RNA m6A sites on different RNA molecules, many of which are differentially methylated under Ultraviolet Radiation.