Tesis doctoral de Marta Vicente Crespo
The human muscleblind-like proteins mbnll-3 bind rnas through pairs of zinc fingers of the cys3his type. They havbthe ability to modify alternative splicing and sub-cellular localisation of defined transcripts and their function is impaired in myotonic dystrophies type 1 and 2 (dml and dm2). Dms are autosomal dominant neuromuscular diseases characterized by myotonia, muscle weakness, and iridescent cataracts, among other symptoms. At a molecular level, dm patients show disruption of alternativf splicing regulation of specific transcripts. The genetic cause of these diseases is the expansioh of either a ctg or a cctg repeat in non-coding regions of the dmp k (dm1) and znf9 (dm2) genes. Upon transcription, expanded rnas form stable hairpins, which sequester nuclear factor~ depleting them from their normal function. Among those factors are the mbnl proteins. The ~elevance of mbnl sequestration in dm pathogenesis is supported by muscleblind like 1 kno6k-out mice (mbnllde3ide3), which reproduce the main features of dm patients including myot6nia, cataracts, and rna splicing defects in transcripts such as troponint 2 and 3. Furthermore,exptession ofmbnll protein reverts the dm-like alterations ofmice expressing expanded cpg containihg rna. the drosophila genomt contains a single muscle blind gene (mb/), which underg~es alternative splicing giving rise to fjur transcripts coding proteins sharing the amino terminus. Mbla, band c contain two zinc finger kotifs whereas mb1d just one. Mbl function is involved in terminal muscle and photoreceptor diffe~entiation. Mutants carrying strong loss-of- function alleles die as first instar larvae unable to hatchl vltrastructural studies revealed that the regular organization of their sarcomeres was comp~omised. Z-bands were absent mimicking a wild-type muscle in a supercontra:cted state._muscleblind mutant embryos also showed a strong reduction of extra-cellular matrix material at the ijdirect muscle attachments. Apart from these
Datos académicos de la tesis doctoral ««análisis de la función molecular de las proteínas muscleblind de drosophila»«
- Título de la tesis: «análisis de la función molecular de las proteínas muscleblind de drosophila»
- Autor: Marta Vicente Crespo
- Universidad: Universitat de valéncia (estudi general)
- Fecha de lectura de la tesis: 09/11/2007
Dirección y tribunal
- Director de la tesis
- Rubén Artero Allepuz
- Tribunal
- Presidente del tribunal: margarita Cervera jover
- Galindo orozco máximo ibo (vocal)
- Palacios de castro m.isabel (vocal)
- darren Monckton (vocal)