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How many antiviral small interfering RNAs may be encoded by the mammalian genomes?

Zabolotneva A, Tkachev V, Filatov F, Buzdin A - Biol. Direct (2010)

Bottom Line: It was found that >50% of the human genome is transcribed in different cell types and that these transcripts are mainly not associated with known protein coding genes, but represent non-coding RNAs of unknown functions.Provided that these processed target motifs may be complementary to viral transcripts, fixation of the repeats into the host genome may be of a considerable benefit to the host.Shpakovski.

View Article: PubMed Central - HTML - PubMed

Affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya st, Moscow 117997, Russia.

ABSTRACT

Background: The discovery of RNA interference phenomenon (RNAi) and understanding of its mechanisms has revolutionized our views on many molecular processes in the living cell. Among the other, RNAi is involved in silencing of transposable elements and in inhibition of virus infection in various eukaryotic organisms. Recent experimental studies demonstrate few cases of viral replication suppression via complementary interactions between the mammalian small RNAs and viral transcripts.

Presentation of the hypothesis: It was found that >50% of the human genome is transcribed in different cell types and that these transcripts are mainly not associated with known protein coding genes, but represent non-coding RNAs of unknown functions. We propose a hypothesis that mammalian DNAs encode thousands RNA motifs that may serve for antiviral protection. We also presume that the evolutional success of some groups of genomic repeats and, in particular, of transposable elements (TEs) may be due to their ability to provide antiviral RNA motifs to the host organism. Intense genomic repeat propagation into the genome would inevitably cause bidirectional transcription of these sequences, and the resulting double-stranded RNAs may be recognized and processed by the RNA interference enzymatic machinery. Provided that these processed target motifs may be complementary to viral transcripts, fixation of the repeats into the host genome may be of a considerable benefit to the host. It fits with our bioinformatical data revealing thousands of 21-28 bp long motifs identical between human DNA and human-pathogenic adenoviral and herpesviral genomes. Many of these motifs are transcribed in human cells, and the transcribed part grows proportionally to their lengths. Many such motifs are included in human TEs. For example, one 23 nt-long motif that is a part of human abundant Alu retrotransposon, shares sequence identity with eight human adenoviral genomes.

Testing the hypothesis: This hypothesis could be tested on various mammalian species and viruses infecting mammalian cells.

Implications of the hypothesis: This hypothesis proposes that mammalian organisms may use their own genomes as sources of thousands of putative interfering RNA motifs that can be recruited to repress intracellular pathogens like proliferating viruses.

Reviewers: This article was reviewed by Eugene V. Koonin, Valerian V. Dolja and Yuri V. Shpakovski.

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Related in: MedlinePlus

Human genome contains sequence motifs identical to the DNAs of human adenoviruses. Human adenovirus types are shown on abscises axis. Histogram represents numbers of 21-, 22-, 23-, 24-, 25-, 26-, 27-, 28- and 29 nucleotide long sequence motifs identical between human and adenoviral genomes. Complete human adenovirus genome sequences were extracted from GenBank. Quantization of perfectly matching nucleotide motifs was done using the BLAST Web-server at NCBI [44].
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Figure 1: Human genome contains sequence motifs identical to the DNAs of human adenoviruses. Human adenovirus types are shown on abscises axis. Histogram represents numbers of 21-, 22-, 23-, 24-, 25-, 26-, 27-, 28- and 29 nucleotide long sequence motifs identical between human and adenoviral genomes. Complete human adenovirus genome sequences were extracted from GenBank. Quantization of perfectly matching nucleotide motifs was done using the BLAST Web-server at NCBI [44].

Mentions: We performed a bioinformatic assay aimed to quantify in human DNA sequence motifs that perfectly match on 26 published adenoviral genomes (Figure 1). Human adenoviral genomes have similar lengths of ~34-36 kb and encode each for approximately 35 viral genes [39]. Only different nucleotide motifs were taken into account, motifs repeated in human or adenoviral genome several times were considered as a sole motif. Each motif was quantified only once, e.g. 25 nt-long sequence was registered only as one 25 nt-long motif, but not also as 24-, 23-, 22- and 21 nt-long motifs.


How many antiviral small interfering RNAs may be encoded by the mammalian genomes?

Zabolotneva A, Tkachev V, Filatov F, Buzdin A - Biol. Direct (2010)

Human genome contains sequence motifs identical to the DNAs of human adenoviruses. Human adenovirus types are shown on abscises axis. Histogram represents numbers of 21-, 22-, 23-, 24-, 25-, 26-, 27-, 28- and 29 nucleotide long sequence motifs identical between human and adenoviral genomes. Complete human adenovirus genome sequences were extracted from GenBank. Quantization of perfectly matching nucleotide motifs was done using the BLAST Web-server at NCBI [44].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2992506&req=5

Figure 1: Human genome contains sequence motifs identical to the DNAs of human adenoviruses. Human adenovirus types are shown on abscises axis. Histogram represents numbers of 21-, 22-, 23-, 24-, 25-, 26-, 27-, 28- and 29 nucleotide long sequence motifs identical between human and adenoviral genomes. Complete human adenovirus genome sequences were extracted from GenBank. Quantization of perfectly matching nucleotide motifs was done using the BLAST Web-server at NCBI [44].
Mentions: We performed a bioinformatic assay aimed to quantify in human DNA sequence motifs that perfectly match on 26 published adenoviral genomes (Figure 1). Human adenoviral genomes have similar lengths of ~34-36 kb and encode each for approximately 35 viral genes [39]. Only different nucleotide motifs were taken into account, motifs repeated in human or adenoviral genome several times were considered as a sole motif. Each motif was quantified only once, e.g. 25 nt-long sequence was registered only as one 25 nt-long motif, but not also as 24-, 23-, 22- and 21 nt-long motifs.

Bottom Line: It was found that >50% of the human genome is transcribed in different cell types and that these transcripts are mainly not associated with known protein coding genes, but represent non-coding RNAs of unknown functions.Provided that these processed target motifs may be complementary to viral transcripts, fixation of the repeats into the host genome may be of a considerable benefit to the host.Shpakovski.

View Article: PubMed Central - HTML - PubMed

Affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya st, Moscow 117997, Russia.

ABSTRACT

Background: The discovery of RNA interference phenomenon (RNAi) and understanding of its mechanisms has revolutionized our views on many molecular processes in the living cell. Among the other, RNAi is involved in silencing of transposable elements and in inhibition of virus infection in various eukaryotic organisms. Recent experimental studies demonstrate few cases of viral replication suppression via complementary interactions between the mammalian small RNAs and viral transcripts.

Presentation of the hypothesis: It was found that >50% of the human genome is transcribed in different cell types and that these transcripts are mainly not associated with known protein coding genes, but represent non-coding RNAs of unknown functions. We propose a hypothesis that mammalian DNAs encode thousands RNA motifs that may serve for antiviral protection. We also presume that the evolutional success of some groups of genomic repeats and, in particular, of transposable elements (TEs) may be due to their ability to provide antiviral RNA motifs to the host organism. Intense genomic repeat propagation into the genome would inevitably cause bidirectional transcription of these sequences, and the resulting double-stranded RNAs may be recognized and processed by the RNA interference enzymatic machinery. Provided that these processed target motifs may be complementary to viral transcripts, fixation of the repeats into the host genome may be of a considerable benefit to the host. It fits with our bioinformatical data revealing thousands of 21-28 bp long motifs identical between human DNA and human-pathogenic adenoviral and herpesviral genomes. Many of these motifs are transcribed in human cells, and the transcribed part grows proportionally to their lengths. Many such motifs are included in human TEs. For example, one 23 nt-long motif that is a part of human abundant Alu retrotransposon, shares sequence identity with eight human adenoviral genomes.

Testing the hypothesis: This hypothesis could be tested on various mammalian species and viruses infecting mammalian cells.

Implications of the hypothesis: This hypothesis proposes that mammalian organisms may use their own genomes as sources of thousands of putative interfering RNA motifs that can be recruited to repress intracellular pathogens like proliferating viruses.

Reviewers: This article was reviewed by Eugene V. Koonin, Valerian V. Dolja and Yuri V. Shpakovski.

Show MeSH
Related in: MedlinePlus