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regulatory circuit of human microrna biogenesis监管人类微rna生物起源的电路
Regulatory Circuit of Human MicroRNA
Biogenesis
1,2 1 1 1,3*
Ji Lee , Zhihua Li , Rachel Brower-Sinning , Bino John
1 Department of Computational Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America, 2 Department of Bioengineering,
Pennsylvania State University, University Park, Pennsylvania, United States of America, 3 University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States of
America
miRNAs (microRNAs) are a class of endogenous small RNAs that are thought to negatively regulate protein production.
Aberrant expression of many miRNAs is linked to cancer and other diseases. Little is known about the factors that
regulate the expression of miRNAs. We have identified numerous regulatory elements upstream of miRNA genes that
are likely to be essential to the transcriptional and posttranscriptional regulation of miRNAs. Newly identified
regulatory motifs occur frequently and in multiple copies upstream of miRNAs. The motifs are highly enriched in G and
C nucleotides, in comparison with the nucleotide composition of miRNA upstream sequences. Although the motifs
were predicted using sequences that are upstream of miRNAs, we find that 99% of the top-predicted motifs
preferentially occur within the first 500 nucleotides upstream of the transcription start sites of protein-coding genes;
the observed preference in location underscores the validity and importance of the motifs identified in this study. Our
study also raises the possibility that a considerable number of well-characterized, disease-associated transcription
factors (TFs) of protein-coding genes contribute to the abnormal miRNA expression in diseases such as cancer. Further
analysis of predicted miRNA–protein interac
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