Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Genes encoding replication-dependent histones lack introns, and the mRNAs produced are a unique class of RNA polymerase II transcripts in eukaryotic cells that do not end in a polyadenylated tail.
This study highlights for the first time the deregulation of replication-dependent histone gene expression and its involvement in ALS. During the evolution of eukaryotes, molecular mechanisms were established to ensure accurate assembly of newly replicated DNA into chromatin. Therefore, in the S phase of the cell cycle, DNA synthesis is tightly coupled with histone protein synthesis.
These two processes are finely balanced, as any disturbance may result in dysregulation of gene expression, cell cycle arrest, and chromosome instability, which may lead to developmental failure 1. This coordination is most sophisticated in higher eukaryotes. At the end of the S phase, the availability of histones is repressed because an excess could be harmful to the cells 2. Additionally, several of these factors are cell cycle-regulated, and their highest activity is in the S phase of the cell cycle 7 , 8 , 9.
This protein plays a role in genomic maintenance and DNA recombination 18 , 19 , 20 , in addition to regulating RNA metabolism and processing.
These processes include transcription, splicing, alternative splicing, miRNA biogenesis and nucleocytoplasmic shuttling of mRNAs 20 , 21 , 22 , 23 , In human neurons, FUS is located at synaptic sites along dendrites and has an important function in transporting mRNA for local translation, as well as its involvement in synaptic plasticity 25 , ALS is a chronic, progressive and uniformly fatal neurodegenerative disorder affecting motor neurons in the brain and spinal cord.
