Splicing signals in the human hemoglobin genes at the sequence and folding levels

Abstract

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.Splice site prediction is a critical and tough issue for defining the protein-coding sequences in eukaryotic genome sequences [1,2] . Although more than 98% of the introns start at GU and end at AG, the problem lies in selecting the correct splice sites from many GUs and AGs in a pre-mRNA [3] . For example, there are 87 GUs and 81 AGs in HBB pre-mRNAs, but only two GU-AG pairs are the authentic splice sites. Given the advances in splicing motif, branch site, and splicing enhancers and silencers, it is still unclear how to recognize the splice sites precisely.A good candidate for exploring the mechanisms of splice site recognition is the human hemoglobin (Hb) gene family, which comprises ten genes in two clusters: all the five α-type genes cluster tightly at the chromosome position 16p13.3 in the order of HBZ, HBM, HBA2, HBA1, and HBQ1 [4,5] and the other five β-type genes at 11p15.5, in the order of HBE1, HBG2, HBG1, HBD, and HBB. These short genes contain two introns, dividing the coding sequences into three parts, as well as the two terminal non-translational regions, where we denoted the seven regions as 5'u, cd1, in1, cd2, in2, cd3, and 3'u, for the 5'-untranslated region, coding sequence 1, intron 1, coding sequence 2, intron 2, coding sequence 3, and 3'-untranslated region, respectively.Recognition of the human Hb pre-mRNA splice

Design of Map Positioning and Navigation System Based on Mobile Platform

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