Methods and compositions are provided which allow for a single microRNA (miRNA) to reduce the level of expression of at least two members of the same protein and/or gene family. Such methods and compositions employ miRNA expression constructs having a structure such that the most abundant form of miRNA produced from the construct is a 22-nucleotide miRNA. The 22-nucleotide miRNA produced from the miRNA expression construct thereby reduces the level of expression of not only the target sequence for the miRNA, but also reduces the level of expression of at least one additional sequence from the same protein and/or gene family as the target sequence.
