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Frequency and fate of microRNA editing in human brain

Kawahara, Yukio, Megraw, Molly, Kreider, Edward, Iizasa, Hisashi, Valente, Louis, Hatzigeorgiou, Artemis G., Nishikura, Kazuko·2008·Nucleic Acids Research
DOI 10.1093/nar/gkn479PMC PMC2532740
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Abstract

Primary transcripts of certain microRNA (miRNA) genes (pri-miRNAs) are subject to RNA editing that converts adenosine to inosine (A→I RNA editing). However, the frequency of the pri-miRNA editing and the fate of edited pri-miRNAs remain largely to be determined. Examination of already known pri-miRNA editing sites indicated that adenosine residues of the UAG triplet sequence might be edited more frequently. In the present study, therefore, we conducted a large-scale survey of human pri-miRNAs containing the UAG triplet sequence. By direct sequencing of RT-PCR products corresponding to pri-miRNAs, we examined 209 pri-miRNAs and identified 43 UAG and also 43 non-UAG editing sites in 47 pri-miRNAs, which were highly edited in human brain. In vitro miRNA processing assay using recombinant Drosha-DGCR8 and Dicer-TRBP (the human immuno deficiency virus transactivating response RNA-binding protein) complexes revealed that a majority of pri-miRNA editing is likely to interfere with the miRNA processing steps. In addition, four new edited miRNAs with altered seed sequences were identified by targeted cloning and sequencing of the miRNAs that would be processed from edited pri-miRNAs. Our studies predict that ∼16% of human pri-miRNAs are subject to A→I editing and, thus, miRNA editing could have a large impact on the miRNA-mediated gene silencing.

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  • Several of these miRNA variants (miR-376 family members, miR-411, miR-379, and miR-320a) have previously been described in deep sequencing studies on human brain and are not specific to glioblastoma.

    “Furthermore, several of these miRNA variants (miR-376 family members, miR-411, miR-379, and miR-320a) have previously been described in deep sequencing studies performed on human brain [36], [37], and therefore, are not specific to glioblastoma.”

    From Reduced Expression of Brain-Enriched microRNAs in Glioblastomas Permits Targeted Regulation of a Cell Death Gene (2011) · cites this paper as [36]

  • A to G changes occurred in >60% of the reads for members of the miR-376 family (miR-376a, b, and c) at nucleotide position six of the mature miRNA sequence.

    “Congruent with previous studies, A to G changes occurred in >60% of the reads for members of the miR-376 family (miR-376a, b, and c) at nucleotide position six of the mature miRNA sequence (Table 1, Fig. S3A) [36].”

    From Reduced Expression of Brain-Enriched microRNAs in Glioblastomas Permits Targeted Regulation of a Cell Death Gene (2011) · cites this paper as [36]

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Metadata

Authors
Kawahara, Y., Megraw, M., Kreider, E., Iizasa, H., Valente, L., Hatzigeorgiou, A. G., & Nishikura, K.
Affiliations
  • The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
  • Department of Genetics, School of Medicine, University of Pennsylvania Philadelphia, PA 19104, USA
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2008-08-06
Volume
36
Issue
16
Pages
5270-5280
ISSN
  • 1362-4962
  • 0305-1048
DOI
10.1093/nar/gkn479
PMC
PMC2532740
Cited by
325
References
5
Language
en
Licence
creativecommons.org/licenses/by-nc/2.0/uk/ (vor, 4744 d)
Funders
  • National Institutes of Health (CA72764, GM-40536, GM079091, P30 CA10815)
  • Juvenile Diabetes Research Foundation (1-2006-210)
  • Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health
  • National Institutes of Health Postdoctoral Supplemental Award (L070045)
  • NCI National Institutes of Health Postdoctoral Training Grant (CA09171)

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