Quantitative analysis questions the role of MeCP2 as a global regulator of alternative splicing

English version

Autoři: Kashyap Chhatbar ^aff001; Justyna Cholewa-Waclaw ^aff002; Ruth Shah ^aff002; Adrian Bird ^aff002; Guido Sanguinetti ^aff001
Působiště autorů: School of Informatics, University of Edinburgh, Edinburgh, United Kingdom ^aff001; The Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom ^aff002; International School for Advanced Studies (SISSA), Trieste, Italy ^aff003
Vyšlo v časopise: Quantitative analysis questions the role of MeCP2 as a global regulator of alternative splicing. PLoS Genet 16(10): e32767. doi:10.1371/journal.pgen.1009087
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009087

Souhrn

MeCP2 is an abundant protein in mature nerve cells, where it binds to DNA sequences containing methylated cytosine. Mutations in the MECP2 gene cause the severe neurological disorder Rett syndrome (RTT), provoking intensive study of the underlying molecular mechanisms. Multiple functions have been proposed, one of which involves a regulatory role in splicing. Here we leverage the recent availability of high-quality transcriptomic data sets to probe quantitatively the potential influence of MeCP2 on alternative splicing. Using a variety of machine learning approaches that can capture both linear and non-linear associations, we show that widely different levels of MeCP2 have a minimal effect on alternative splicing in three different systems. Alternative splicing was also apparently indifferent to developmental changes in DNA methylation levels. Our results suggest that regulation of splicing is not a major function of MeCP2. They also highlight the importance of multi-variate quantitative analyses in the formulation of biological hypotheses.

Klíčová slova:

Alternative splicing – Developmental neuroscience – DNA methylation – Gene expression – Gene regulation – Neurons – RNA sequencing – RNA splicing

Zdroje

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