Mechanistic characterization of the HDV genomic ribozyme: the cleavage site base pair plays a structural role in facilitating catalysis.

ABSTRACT: The hepatitis delta virus (HDV) ribozyme occurs in the genomic and antigenomic strands of the HDV RNA and within mammalian transcriptomes. Previous kinetic studies suggested that a wobble pair (G*U or A(+)*C) is preferred at the cleavage site; however, the reasons for this are unclear. We conducted sequence comparisons, which indicated that while G*U is the most prevalent combination at the cleavage site, G-C occurs to a significant extent in genomic HDV isolates, and G*U, G-C, and A-U pairs are present in mammalian ribozymes. We analyzed the folding of genomic HDV ribozymes by free energy minimization and found that variants with purine-pyrimidine combinations at the cleavage site are predicted to form native structures while pyrimidine-purine combinations misfold, consistent with earlier

SUBMITTER: Cerrone-Szakal AL 

PROVIDER: S-EPMC2525964 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature