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. While a single 21 base pair miRNA can cause cleavage of a variety of species of mRNAs, an entire gene family cannot be silenced unless that gene family shares near identity within a 21 base pair region that is also able to be cleaved by a single miRNA. In certain embodiments, all members of a given protein and/or gene family can be suppressed with a miRNA expression construct disclosed herein even if they do not share near identity within a 21 base pair region that is also able to function as a miRNA. 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.