text: Scientists use a number of methods to study the complex structures and functions of the 3′ UTR. Even if a given 3′-UTR in an mRNA is shown to be present in a tissue, the effects of localization, functional half-life, translational efficiency, and trans-acting elements must be determined to understand the 3′-UTR's full functionality. Computational approaches, primarily by sequence analysis, have shown the existence of AREs in approximately 5 to 8% of human 3′-UTRs and the presence of one or more miRNA targets in as many as 60% or more of human 3′-UTRs. Software can rapidly compare millions of sequences at once to find similarities between various 3′ UTRs within the genome. Experimental approaches have been used to define sequences that associate with specific RNA-binding proteins; specifically, recent improvements in sequencing and cross-linking techniques have enabled fine mapping of protein binding sites within the transcript. Induced site-specific mutations, for example those that affect the termination codon, polyadenylation signal, or secondary structure of the 3′-UTR, can show how mutated regions can cause translation deregulation and disease. These types of transcript-wide methods should help our understanding of known cis elements and trans-regulatory factors within 3′-UTRs.