We propose ExSpeU1s as a novel therapeutic strategy to correct, in several human disorders, different types of splicing mutations associated with defective exon definition.
Interestingly, a patient with RAB27A mutations presented with defective NK and CD8+ T cell exocytosis, but normal NK cell cytotoxicity, while a patient with LYST mutations displayed defective NK cell cytotoxicity but only abnormal NK and CD8+ T-cell exocytosis (Fig. 2a, d, e).
Certain ACD mutations were associated with defective dimerization, increased chaperone activity, and improved heat stress tolerance [30].
Although many mutant receptors with defective trafficking and/or insulin binding and/or signal transduction have been described, mutations predominantly affecting receptor endocytosis or recycling are rare.
To uncover novel activities required for maximal gene expression in response to osmostress, we undertook an exhaustive genome-wide genetic screen searching for mutations that rendered cells with defective expression of an osmoresponsive gene reporter at high osmolarity.
We have previously shown that the mcl1 mutant shows genetic interactions with mutations defective in Okazaki fragment maturation such as rad2 (Rand7/FEN1) andna2and and it accumulates double strand breaks after completion of bulk DNA synthesis, suggesting that Mcl1 is involved in lagging strand DNA synthesis [29].
Cytochrome c with a K72A mutation is defective in interaction with Apaf-1, but retains its respiration-associated function (Yu et al., 2001).
Patients with defective COQ2 mutations were shown to have GCI-positive oligodendroglia [ 23], providing direct evidence for a role of mitochondrial dysfunction in MSA pathogenesis.
Mutations in nuclear genes associated with defective complex III (cIII) of the mitochondrial respiratory chain are rare, having been found in only two cIII assembly factors and, as private changes in single families, three cIII structural subunits.
in addition, patients with OPA1 mutation showed defective mitochondrial ATP production in skeletal muscle.
