Algorithmic Research Of Discovering Human Encoded MiRNAs That Regulate The Influenza Virus Genome

MicroRNAs (miRNAs) are small, noncoding and single-stranded RNA molecules,-22 nucleotides in length. MiRNAs exist in eukaryotic genomes widely and are quite conservative. They can downregulate gene expression:mRNA cleavage or translational repression by complementarity between 3'untranslated region (UTR) of mRNA and seed region of miRNA (nucleotides 1-8 of 5'end). In mammals, miRNAs usually repress translation, and in plants, they usually specify cleavage. MiRNAs involve in a variety of biological processes such as cell proliferation, apoptosis, cell differentiation, et al., and they play a regulatory role in a variety of biological networks. In recent years, research on miRNAs has been a hot spot.Influenza viruses are part of the family Orthomyxoviridae, and they are the single-negative strand RNA viruses. Influenza can cause acute upper respiratory tract infection and spread rapidly in the air, which also can cause periodic pandemic in the world. Influenza viruses can be divided into A, B and C based on antigenic differences of nucleoprotein and matrix protein. According to antigenic differences of hemagglutinin and neuraminidase, they can be divided into 16 subtypes H1-H16 and 9 subtypes N1-N9. The novel influenza emerged in Mexico, the United States, and several other nations in 2009, is known as influenza A/H1N1. Genome of influenza virus A and B have 8 segments, and genome of C has 7 segments, which encode proteins that are necessary in the viral replication cycle. Because influenza viruses only replicate within living cells, they are closely related with the host cells. The current approach to inhibit the influenza virus is vaccine, but the mutation speed of the viruses is rapid, vaccine production speed can not keep up with the mutation. Researchers have been suppressed influenza infection by RNA interference.Although researchers have adopted the method of biological experiments, cDNA microarray techniques and other methods to discovery regulation mechanism between host and viruse, regulation mechanism of miRNA in viral infection is still in its infancy. Because biological experiments have lots of shortcomings, researchers have discovered the potential binding sites between human encoded miRNAs and H5N1 segments (PB2 and HA) by the method of computation. And the binding regions of miRNA are quite conservative in the different strain. Here we propose a new algorithm called miRBase which is based on scoring to discover human encoded miRNAs that regulate the influenza virus genome.In this paper, H1N1 is taken as an example, the data of H1N1 from the year 2000 to 2009 on NCBI and mature sequences of human encoded miRNA on miRBase are used. There are three steps are in miRScore:Scoring based on the same complementary sites for the sequences of the year 2009.Scoring based on the consensus secondary structure of all sequences.Scoring based on conservative measure of the same complementary sites for the sequences of the year 2000 to 2008.After the scoring, after computing the mean value of socres, take the human encoded miRNAs with the scores greater than the mean value as the results, and the human encoded miRNA which is most likely to regulate influenza virus genome is the one with the highest score. The number of human encoded miRNAs with the scores greater than the mean value is:10 for HA,3 for MP,6 for NA,5 for NP,2 for NS,11 for PA,9 for PB1 and 2 for PB2. Two miRNAs for HA, PA and PB1 have two binding sites respectively, one miRNA for PB2 segment has two sites, and the miRNAs of other segments have one site. The binding sites and matching are also obtained through the experiment.In miRScore, step 1 and step2 are essential. Taking the consensus secondary structure as an important factor is one of the innovation points in this paper, and conservative measure makes results more significant.The results in this paper are still needed to be further verified by biological experiments, but the scope of experiments has been reduced greatly, so experiments are no longer blind and trial. A lot of manpower and resources are saved, and saving time is another more important thing. Currently, the role of miRNAs in viral infection is still in the initial stage, this paper provieds a theoretical basis for drug design and reduces the cycle of design effectively, this paper are important for the research on prevention of influenza viruses.