Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation
Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation
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作者：
Hu, J;Lutz, CS;Tian, B
多聚腺苷酸化是真核生物中几乎所有细胞mRNA成熟的重要步骤。在人类细胞中，大多数poly（A）位点的侧翼是上游的AAUAAA六聚体或接近的变体，以及下游的富含U/GU的元件。在酵母和植物中，已经发现另外的顺式元件位于poly（A）位点的上游，包括UGUA、UAUA和富含U的元件。在这项研究中，我们已经开发了一个名为PROBE（聚腺苷酸化相关的寡核苷酸二维富集）的计算机程序，以确定顺式元件，可能发挥调节作用的mRNA聚腺苷酸化。通过比较人类基因组中常用的poly（A）位点和不常用的poly（A）位点周围的序列，我们发现酵母和植物中存在的顺式元件也存在于人类poly（A）区域，包括上游富含U的元件，以及UAUA和UGUA元件。此外，还发现了几个新的元件与人类poly（A）位点相关，包括几个富含G的元件。因此，我们认为许多顺式元件在真核生物中是进化保守的，并且人poly（A）位点具有另外一组可能参与mRNA聚腺苷酸化调节的顺式元件。
Polyadenylation is an essential step for the maturation of almost all cellular mRNAs in eukaryotes. in human cells, most poly(A) sites are flanked by the upstream AAUAAA hexamer or a close variant, and downstream U/GU-rich elements. In yeast and plants, additional cis elements have been found to be located upstream of the poly(A) site, including UGUA, UAUA, and U-rich elements. In this study, we have developed a computer program named PROBE (Polyadenylation-Related Oligonucleotide Bidimensional Enrichment) to identify cis elements that may play regulatory roles in mRNA polyadenylation. By comparing human genomic sequences surrounding frequently used poly(A) sites with those surrounding less frequently used ones, we found that cis elements occurring in yeast and plants also exist in human poly(A) regions, including the upstream U-rich elements, and UAUA and UGUA elements. In addition, several novel elements were found to be associated with human poly(A) sites, including several G-rich elements. Thus, we suggest that many cis elements are evolutionarily conserved among eukaryotes, and human poly(A) sites have an additional set of cis elements that may be involved in the regulation of mRNA polyadenylation.