Single nucleotide polymorphism is an interesting problem that can alter gene expression,recode amino acids and affect protein function.Protein structural changes have generally been attributed to amino acid replacements,and only a few research efforts have examined the effects of mRNA structural changes to the conformation of the corresponding protein coded by the mRNA.In the present study,the human β-globin HBB gene and four variants were examined.The mRNA secondary structures were constructed using the dynamic extended folding method and the encoded protein secondary structures were obtained from related databases.Comparisons were performed between these structures before and after mutations were introduced into the mature mRNAs and the proteins.We focused on the structural changes from mRNA to protein and found that regular protein conformations tend to match stable mRNA regions,whereas irregular protein conformations,such as β/γ turns and random coils,often match unstable mRNA regions.Mutations within unstable regions can alter the mRNA secondary structure and leave footprints in the protein structure.Comparison of the mRNA-protein secondary structure relationships represents a potential strategy to explore protein functional changes.
LI YanFeiYE DongHaiZHANG WenWANG ChuanMingLIU CiQuanCAO Huai
Identification of the splice sites is a critical and tough issue in eukaryotic genome annotation. Here, a statistical study is introduced for detecting the splicing signals in the human hemoglobin (Hb) pre-mRNAs by using the approaches of regional pairwise alignment, splicing weight matrix scoring, and dynamic extended folding. First, the regional pairwise alignment results show that the coding regions of the human Hb genes are at a high level for both conservation and fluctuation. Second, the weighted matrix scoring results indicate that, although the authentic splicing motifs are always scored the highest in a sequence, the sequence motif alone is inadequate to precisely define the splice sites. Finally, we deduce the RNA frame structures by applying an extended folding approach to analyze the stable folding elements. We find out that the splice sequences tend to take stretching and partially paired conformations, which benefit recognition and competitive binding of the splicing factors. These results indicate that precise splicing is an integrated effect of multiple mechanisms of signal recognition at the level of sequence and structure.
