Argonaute-Bound Small RNAs from Promoter-Proximal RNA Polymerase II
| Autor: | Timothy J. Kelly, Phillip A. Sharp, Jesse R. Zamudio |
|---|---|
| Přispěvatelé: | Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Zamudio, Jesse Ray, Kelly, Timothy James, Sharp, Phillip A. |
| Rok vydání: | 2014 |
| Předmět: |
Transcription Elongation
Genetic Trans-acting siRNA Biology Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine DNA-directed RNA interference Animals Humans Small nucleolar RNA Promoter Regions Genetic Embryonic Stem Cells 030304 developmental biology Genetics 0303 health sciences Base Sequence Biochemistry Genetics and Molecular Biology(all) Cleavage And Polyadenylation Specificity Factor RNA Argonaute Non-coding RNA Long non-coding RNA 3. Good health RNA silencing Gene Expression Regulation Genetic Techniques Argonaute Proteins RNA Small Untranslated RNA Polymerase II Transcription Initiation Site 030217 neurology & neurosurgery |
| Zdroj: | PMC |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2014.01.041 |
| Popis: | Argonaute (Ago) proteins mediate posttranscriptional gene repression by binding guide miRNAs to regulate targeted RNAs. To confidently assess Ago-bound small RNAs, we adapted a mouse embryonic stem cell system to express a single epitope-tagged Ago protein family member in an inducible manner. Here, we report the small RNA profile of Ago-deficient cells and show that Ago-dependent stability is a common feature of mammalian miRNAs. Using this criteria and immunopurification, we identified an Ago-dependent class of noncanonical miRNAs derived from protein-coding gene promoters, which we name transcriptional start site miRNAs (TSS-miRNAs). A subset of promoter-proximal RNA polymerase II (RNAPII) complexes produces hairpin RNAs that are processed in a DiGeorge syndrome critical region gene 8 (Dgcr8)/Drosha-independent but Dicer-dependent manner. TSS-miRNA activity is detectable from endogenous levels and following overexpression of mRNA constructs. Finally, we present evidence of differential expression and conservation in humans, suggesting important roles in gene regulation. United States. Public Health Service (grant RO1 GM34277) National Cancer Institute (U.S.) (PO1-CA42063) National Cancer Institute (U.S.) (Koch Institute Support (core) grant P30-CA14051) National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (F32GM101872) National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (F32CA139902) |
| Databáze: | OpenAIRE |
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