Short tandem repeats (STRs) have been widely observed, but most STRs have no recognized organization or function. Here we show that for diverse mRNAs. 84% of (GC)(n) repeats were found unexpectedly Coupled with another STR, (GU)(n). These STR couples exhibited preferred polarity and register. In 3' untranslated mRNA sequences (UTRs) 100%, of (GC)(n > 6) repeats were tightly coupled with (GU)(n). For (GC)(n), stem folding energy correlated with the length and number of neighboring, non-folding (GU)(n) partners (p = 0.014). Approximately 20% of (AU)(n greater than or equal to 14) repeats were coupled with (GU)(n). The STR couple (AC)(n)(AG)(n) also exhibited polarity and register preferences. The sequence arrangement at STR-couple joints was conserved rigorously, suggesting that these sequences were under selection pressure. Some STR couples may function as mRNA processing landmarks, based oil alternative transcript comparisons. These observations suggest that some transcribed STRs may be functional UTR signals with predictable organization and usage patterns. (C) 2003 Elsevier Science (USA). All rights reserved.