Simple repeat replacements support similar functions of distinct repeats in inter-species mRNA homologs

Simple repeats are ubiquitous in metazoan genomes, but function has been elusive. We reported that distinct, short tandem repeats (STRs) were coupled with rigorous polarity and register, suggesting order in simple repeat usage. Several STRs that lacked internal, canonical base pairs were associated with mRNAs encoding membrane functions and transcription factors. We hypothesized that diverse, simple repeats, such as (AC)n, (GU)n, (AG)n, (CU)n and (CUUU)n, had similar functions. The hypothesis predicts that closely related mRNAs would sometimes exhibit STR replacements. Comparing aquaporin 3 mRNAs, in rodents and humans, (GU)20 replaced (AG)29. Comparing biglycan mRNAs, (GU)25 replaced (CA)12. Comparing immunoglobulin superfamily member 9 mRNAs, the STR-couple, (CU)17(GU)9 replaced the STR-couple, (GU)19(GC)4. Comparing tumor necrosis factor receptor-21 mRNAs, (GU)24 replaced (CUUU)16. In a collection of 52 rodent-H. sapiens homologous mRNAs that had STRs, six (11.5%) STR-STR replacements occurred, significantly more than expected based on an STR frequency of 0.13% in all reported UTRs (p<0.001). Database studies and the observation of STR replacements among transcript homologs independently support the hypothesis that diverse repeat sequences, such as (AG)n, (AC)n, (GU)n, (CU)n and (CUUU)n, have similar usage that is consistent with analogous functions.