Sequestration of MBNL1 in tissues of patients with myotonic dystrophy type 2

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Publikace nespadá pod Lékařskou fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.
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LUKÁŠ Zdeněk FALK Martin FEIT Josef SOUČEK Ondřej FALKOVÁ Iva ŠTEFANČÍKOVÁ Lenka JANOUŠOVÁ Eva FAJKUSOVÁ Lenka ZAORÁLKOVÁ Jana HRABÁLKOVÁ Renata

Rok publikování 2012
Druh Článek v odborném periodiku
Časopis / Zdroj Neuromuscular Disorders
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://www.sciencedirect.com/science/article/pii/S096089661200082X
Doi http://dx.doi.org/10.1016/j.nmd.2012.03.004
Obor Neurologie, neurochirurgie, neurovědy
Klíčová slova Myotonic dystrophy; Transcription of ZNF9; CCUG repeat expansion; Sequestration of MBNL1 protein; Ribonuclear foci; Insulin receptor alternative splicing
Popis The pathogenesis of myotonic dystrophy type 2 includes the sequestration of MBNL proteins by expanded CCUG transcripts, which leads to an abnormal splicing of their target pre-mRNAs. We have found CCUG(exp) RNA transcripts of the ZNF9 gene associated with the formation of ribonuclear foci in human skeletal muscle and some non-muscle tissues present in muscle biopsies and skin excisions from myotonic dystrophy type 2 patients. Using RNA-FISH and immunofluorescence-FISH methods in combination with a high-resolution confocal microscopy, we demonstrate a different frequency of nuclei containing the CCUG(exp) foci, a different expression pattern of MBNL1 protein and a different sequestration of MBNL1 by CCUG(exp) repeats in skeletal muscle, vascular smooth muscle and endothelia, Schwann cells, adipocytes, and ectodermal derivatives. The level of CCUG(exp) transcription in epidermal and hair sheath cells is lower compared with that in other tissues examined. We suppose that non-muscle tissues of myotonic dystrophy type 2 patients might be affected by a similar molecular mechanism as the skeletal muscle, as suggested by our observation of an aberrant insulin receptor splicing in myotonic dystrophy type 2 adipocytes.

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