Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 4, Pages 1122-1127Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0812210106
Keywords
embryonic stem cells; gene silencing; RNA interference; Xist
Categories
Funding
- National Institutes of Health (NIH) [AI-064345]
- Ruth L. Kirschstein National Research Service Award postdoctoral fellowship [AI-060302]
- Claudia Adams Barr Foundation
- V and Kimmel Scholar Award
- NIH Director's DP2 Award
- California Institute for Regenerative Medicine Young Investigator Award
- Margaret E. Early Trust
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Dicer is central to the RNA interference (RNAi) pathway, because it is required for processing of double-stranded RNA (dsRNA) precursors into small RNA effector molecules. In principle, any long dsRNA could serve as a substrate for Dicer. The X inactive specific transcript (Xist) is an untranslated RNA that is required for dosage compensation in mammals. It coats and silences 1 of the 2 X chromosomes in female cells and initiates a chromosomewide change in chromatin structure that includes the recruitment of Polycomb proteins, but it is largely unknown how Xist RNA mediates these processes. To investigate a potential link between the RNAi pathway and X inactivation, we generated and analyzed Dicer-deficient embryonic stem (ES) cells. In the absence of Dicer, coating by Xist RNA, initiation of silencing, and recruitment of Polycomb proteins occur normally. Dicer ablation had modest effects on the steady-state levels of spliced Xist RNA. Together our data indicate that the RNAi machinery is not essential for the initiation of X inactivation.
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