Out of the loop: Do the proteins bound to an enhancer site on pre-mRNA interact directly with the splice site by diffusion (looping), as is generally accepted, or does the intervening RNA play a role (see scheme)? By inserting a PEG linker between an enhancer sequence and alternative splice sites, the interaction of these two elements can be studied. Intervening RNA was essential for the enhancer activity, which rules out the looping model.