Publication: The fragile X proteins' enigma: to be or not to be nucleolar
About
The Fragile the data supporting this potentially important secondary function.
FMRP is the archetype of a family of cytoplasmic RNA-binding proteins that includes the Fragile X related proteins FXR1P and FXR2P. The primary transcripts of the FMR1 and FXR1, genes undergo alternative splicing processes (Ashley et al., 1993; Verkerk et al., 1993; Sittler et al., 1996; Kirkpatrick et al., 1999), resulting in multiple protein isoforms. Twelve FMRP isoforms have been detected, nine for FXR1P and one for FXR2P. Members of the Fragile X protein family are widely expressed in human tissues and in other mammals, albeit at varying levels, and expression of their isoforms is subtly choreographed (Davidovic et al., 2006a). FMRP is highly abundant in brain and testis but is absent in striated muscles. FXR1P is strongly expressed in striated muscle and testis and lower levels are detected in the brain. FXR2P expression remains almost constant in all organs and tissues. While the FMR1 gene is present on chromosome X, FXR1 and FXR2 are autosomal genes present on chromosome 12 and 17, respectively.
In humans, mutations in the FMR1 gene are the cause of FXS, a neurodevelopmental disorder that is characterized by developmental delay, intellectual disability, and in some cases autism spectrum disorders. FXS clinical presentation is highly heterogeneous. FXS also affects peripheral tissues with patients exhibiting large everted ears, long face, increased cranial circumference, hypotonia, hyperlaxity of ligaments and macroorchidism (Hagerman et al., 2017). The most prevailing hypothesis regarding the physiopathology of FXS is that the absence of functional FMRP causes dysregulation of translation (Bassell and Warren,