Mutations in genes encoding regulators of mRNA decapping and translation initiation: links to intellectual disability.

Mutations in genes encoding regulators of mRNA decapping and translation initiation: links to intellectual disability. Biochem Soc Trans. 2020 May 15;: Authors: Weil D, Piton A, Lessel D, Standart N Abstract Intellectual disability (ID) affects at least 1% of the population, and typically presents in the first few years of life. ID is characterized by impairments in cognition and adaptive behavior and is often accompanied by further delays in language and motor skills, as seen in many neurodevelopmental disorders (NDD). Recent widespread high-throughput approaches that utilize whole-exome sequencing or whole-genome sequencing have allowed for a considerable increase in the identification of these pathogenic variants in monogenic forms of ID. Notwithstanding this progress, the molecular and cellular consequences of the identified mutations remain mostly unknown. This is particularly important as the associated protein dysfunctions are the prerequisite to the identification of targets for novel drugs of these rare disorders. Recent Next-Generation sequencing-based studies have further established that mutations in genes encoding proteins involved in RNA metabolism are a major cause of NDD. Here, we review recent studies linking germline mutations in genes encoding factors mediating mRNA decay and regulators of translation, namely DCPS, EDC3, DDX6 helicase and ID. These RNA-binding proteins have well-established roles in mRNA decapping ...
Source: Biochemical Society Transactions - Category: Biochemistry Authors: Tags: Biochem Soc Trans Source Type: research