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Program > Browse abstracts by author > Fernandes Liane P.

The role of LINE-1 elements in the induction of type I interferon following epigenetic dysregulation
Rocio Enriquez-Gasca  1@  , Poppy A. Gould  2  , Hale Tunbak  3  , James Holt  3  , Liane P. Fernandes  4  , Alba Herrero Del Valle  5  , Xi Wang  6  , Sun Hur  6  , Yorgo Modis  5  , Helen Rowe  3  
1 : The Francis Crick Institute [London]
1 Midland Road, NW1 1AT -  United Kingdom
2 : NYU Langone Health [New York]
301 East 17th Street, Suite 1410, New York, NY 10003 -  United States
3 : Queen Mary University of London
Mile End Road, London E1 4NS -  United Kingdom
4 : Dynamique de la Chromatine [Institut Curie]
Dynamique du noyau [Institut Curie]
26 rue d'Ulm,75248 Paris Cedex 05 -  France
5 : MRC Laboratory of Molecular Biology [Cambridge, UK]
Cambridge Biomedical Campus, Francis Crick Ave, Trumpington, Cambridge CB2 0QH, Royaume-Uni -  United Kingdom
6 : Howard Hughes Medical Institute [Boston]
Harvard Medical School Boston, Massachusetts 02115 -  United States

The impact of Transposable Elements (TEs) in health and disease has been cemented by mounting evidence. Among the multifaceted co-opted functions of these elements is their involvement in immunity. Here, following on from previous work where we showed that the loss of the epigenetic complex - the Human Silencing Hub (HUSH) – can lead to an interferon (IFN) cascade downstream of the dsRNA sensor MDA5, we sought to shed light on the role of Long INterspersed Elements-1 (LINE-1) in nucleic acid sensing. To this end we employed a short hairpin RNA, selected from a panel of shRNAs targeting LINE-1 subfamilies, which is effective at blocking the type I interferon response induced upon inactivation of the chromodomain-containing component of HUSH, MPP8. By performing total RNA-sequencing of IFN reporter cells expressing this hairpin together with shMPP8, we could computationally identify self-RNAs that are candidates for inducing a type I IFN response and which may be involved in autoimmunity. Thus, our results bring us one step closer to disentangling the intricate role of LINE1s in immunity.


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