On the secondary structure in mRNA

The sequence present in DNA phase transcripts have been investigated by Niyogi (1973) using a technique in which mRNA is enzymatically digested to yield different size classes that are resolved chromatographically into populations of equal chain lengths. These chains exhibit specific hybridization to their complementary DNA molecules for lengths N ≥ 10 bases. The stability of the hybrids as a function of temperature has been measured experimentally (Niyogi 1973) and is analyzed theoretically here by a model which treats the hybrids as ensembles of oligomeric DNA-RNA helices of different chain length and random base sequence. Base pairs with G and C residues (rC · dG, rG · dC) are assigned a mean enthalpy and entropy of formation distinct from pairs with A and U or T. The theoretical results predict less sensitivity of the stability of the hybrids to G + C mole fraction than is measured. This behavior is consistent with the presence in longer mRNA fragments of exceptionally stable sequences due to clustering of G · C pairs of purine vs pyrimidine configurations on each strand, or both. The existence of stable hairpin secondary structural configurations in the mRNA's of bacteriophages T2, T5 and T7 explains this in a natural way, suggesting that these mRNA's unconstrained by "packing" structural requirements such as may hold in RNA phase molecules, also possess a significant non-random secondary structure.