Gene length matters in neurons

Abstract

A recent study by Gabel et al. (2015) found that Mecp2, the gene mutated in Rett syndrome, represses long (> 100 kb) genes associated with neuronal physiology and connectivity by binding to methylated CA sites in DNA. This study adds to a growing body of literature implicating gene length and transcriptional mechanisms in neurodevelopmental and neurodegenerative disorders.

Figure 1. The transcriptome of neural tissues is biased for longer transcripts relative to non-neural tissues and cell lines

Mouse expression data were obtained from BioGPS (Su et al., 2004). Expression intensity for each gene in a given tissue was compared to gene length and Pearson correlation coefficients were computed. Positive values indicate a positive correlation between gene expression and gene length.

Figure 2. The transcriptome of neurons is biased for longer transcripts relative to other brain cell types

Oligoden. = oligodendrocytes. Hippocampal CA1 versus somatosensory (SS) pyramidal neurons, *p < 0.005 by two-sample t-test. Error bars are standard error of the mean. Gene expression data were obtained from http://linnarssonlab.org/blobs/cortex/expression_mRNA_17-Aug-2014.txt. Total read counts were computed for each cell by taking the sum of all counts for all RefSeq genes, and individual gene values were normalized by this sum. Genes shorter than 500 bp in length were excluded from the analysis. Gene length Pearson correlations for each of the 3,005 individual cells were then computed. Values were averaged and plotted for each of the nine cell classes as defined in Zeisel et al. (2015).