期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 46, 页码 18097-18102出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0709193104
关键词
miRNA; RNAi; siRNA; repetitive element
资金
- NCI NIH HHS [P30 CA014051, P01-CA42063, P01 CA042063, P30-CA14051] Funding Source: Medline
- NICHD NIH HHS [F32 HD051190, 5-F32-HD051190] Funding Source: Medline
- NIGMS NIH HHS [R01 GM034277, R01-GM34277] Funding Source: Medline
Short RNA expression was analyzed from Dicer-positive and Dicer-knockout mouse embroyonic stem (ES) cells, using high-throughput pyrosequencing. A correlation of miRNA quantification with sequencing frequency estimates that there are 110,000 miRNAs per ES cell, the majority of which can be accounted for by six distinct miRNA loci. Four of these miRNA loci or their human homologues have demonstrated roles in cell cycle regulation or oncogenesis, suggesting that a major function of the miRNA pathway in ES cells may be to shape their distinct cell cycle. Forty-six previously uncharacterized miRNAs were identified, most of which are expressed at low levels and are less conserved than the set of known miRNAs. Low-abundance short RNAs matching all classes of repetitive elements were present in cells lacking Dicer, although the production of some SINE- and simple repeat-associated short RNAs appeared to be Dicer-dependent. These and other Dicer-dependent sequences resembled miRNAs. At a depth of sequencing that approaches the total number of 5'phosphorylated short RNAs per cell, miRNAs appeared to be Dicer's only substrate. The results presented suggest a model in which repeat-associated miRNAs serve as host defenses against repetitive elements, a function canonically ascribed to other classes of short RNA.
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