Sustainable recovery of MBNL activity in autoregulatory feedback loop in myotonic dystrophy.

ABSTRACT: Muscleblind-like proteins (MBNLs) are RNA-binding proteins essential for the developmental regulation of various processes including alternative splicing. Their activity is misregulated in myotonic dystrophy type 1 (DM1), an incurable genetic, neuro-muscular disorder caused by uncontrolled expansion of CTG repeats. Mutant RNAs containing hundreds or thousands of repeats efficiently sequester MBNL proteins. As a consequence, global alternative splicing abnormalities are induced. Importantly, the size of expansion differs significantly not only between patients but also between different parts of the same muscle as a consequence of somatic expansion. One of the potential therapeutic strategies in DM is overexpression of MBNLs. However, gene therapy tools might induce excessive activity of MB

SUBMITTER: Rogalska Z 

PROVIDER: S-EPMC9672890 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature