How does transcription differ from DNA synthesis? The primary difference between transcription and DNA replication is that only a single strand of mRNA is produced during transcription. During DNA replication both strands need to be copied and DNA polymerase needs to work on both strands at the same time.Because DNA polymerase can only add new bases onto the free 3’ end of a molecule the two strands cannot be synthesized in the same way.ow does transcription differ from DNA synthesis? The primary difference between transcription and DNA replication is that only a single strand of mRNA is produced during transcription. During DNA replication both strands need to be copied and DNA polymerase needs to work on both strands at the same time.