PTBP1 acts as a dominant repressor of the aberrant tissue-specific splicing of ISCU in hereditary myopathy with lactic acidosis.

ABSTRACT:

Background

Hereditary myopathy with lactic acidosis (HML) is an autosomal recessive disease caused by an intron mutation in the iron-sulfur cluster assembly (ISCU) gene. The mutation results in aberrant splicing, where part of the intron is retained in the final mRNA transcript, giving rise to a truncated nonfunctional ISCU protein. Using an ISCU mini-gene system, we have previously shown that PTBP1 can act as a repressor of the mis-splicing of ISCU, where overexpression of PTBP1 resulted in a decrease of the incorrect splicing. In this study, we wanted to, in more detail, analyze the role of PTBP1 in the regulation of endogenous ISCU mis-splicing.

Methods

Overexpression and knockdown of PTBP1 was performed in myoblasts from two HML patients and a healthy control. Quantifica

SUBMITTER: Rawcliffe DFR 

PROVIDER: S-EPMC6305642 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature