Work

Intersection of the RNA Interference and X-Inactivation Pathways

Year: 2008

Type: article

Abstract: In mammals, dosage compensation is achieved by X-chromosome inactivation (XCI) in the female. The noncoding Xist gene initiates silencing of the X chromosome, whereas its antisense partner Tsix blocks silencing. The complementarity of Xist and Tsix RNAs has long suggested a role for RNA interference (RNAi). Here, we report that murine Xist and Tsix form duplexes in vivo. During XCI, the duplexes are processed to small RNAs (sRNAs), most likely on the active X (Xa) in a Dicer-dependent manner. Deleting Dicer compromises sRNA production and derepresses Xist. Furthermore, without Dicer, Xist RNA cannot accumulate and histone 3 lysine 27 trimethylation is blocked on the inactive X (Xi). The defects are partially rescued by truncating Tsix. Thus, XCI and RNAi intersect, down-regulating Xist on Xa and spreading silencing on Xi.

Source: Science

DOI: 10.1126/science.1157676

Authors: Yuya Ogawa, Bryan K. Sun, Jeannie T. Lee

Institutions: Howard Hughes Medical Institute, Harvard University, Massachusetts General Hospital

Language: English

Topic: Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Howard Hughes Medical Institute, National Institute of General Medical Sciences

Award: Regulation of X-chromosome inactivation and imprinting by non-coding elements