Multiple functions of RNAi pathway in mouse Embryonic stem cells

Constance Ciaudo Swiss Federal Institute of Technology Zurich, Department of Biology, Chair of RNAi and Genome Integrity, Zurich, Switzerland

Versione stampabile

May 16 2014
Maso Seminar Room, Via delle Regole n. 101, 38123 Mattarello (TN)

2.30 p.m.

A basal network of gene regulation orchestrates the processes
ensuring maintenance of cellular identity and genome integrity. Long
interspersed elements 1 (L1) are non-long-terminal-repeat retrotransposons
that dominate the mouse genomic landscape, and are expressed in germ
cells, during early development and in mouse Embryonic Stem Cells
(mESCs). In particular, L1 elements continue to affect our genome, and their
movement can lead to sporadic cases of disease. We recently established a
role for RNA interference and other epigenetic pathways in the regulation of
L1 transcription and mobilization. These results shed new light on L1 biology,
uncover defensive, in addition to regulatory roles for RNA interference (RNAi)
pathways. Finally, we also investigate the role of RNAi pathway to protect
mESCs against RNA virus infections and show a novel defensive role for
endogenous siRNA pathways. In this context, we contend that siRNA-based
RNAi has persisted in vertebrates as a primordial mechanism that protects
progenitor cells of developing and adult organisms against the harmful effects
of transposons and exogenous viruses.
This proposed RNAi-based defense is
anticipated to be important, because genomic instability or viral infections in
progenitor cells would have long-lasting detrimental consequences throughout
the entire lineages derived from them.