A new mechanism for reading extra-long genes in neurons

Neurons express genes that are exceedingly long, up to 2 million base pairs, which are crucial for forming synapses and neural circuits. Genetic information is typically transcribed from DNA into RNA, a process that takes longer for larger genes. Regulation of gene expression also occurs at multiple stages. Researchers from Ehime University have discovered that a protein called SFPQ, which binds RNA, forms condensates inside the nucleus of neurons to aid in reading these long genes.

These condensates are membraneless structures that gather specific molecules together. By using super-resolution microscopy, the team found that SFPQ condensates form meshwork-like scaffold structures around RNA, bringing together key components for transcription, splicing, and chromatin regulation. When SFPQ condensates fail to form, the reading of extra-long genes is incomplete, splicing is disrupted, and gene expression is reduced.

This suggests that SFPQ condensates function as a shared workspace to coordinate several processes necessary for the proper functioning of exceptionally long genes. The study sheds light on the physical basis of transcriptional elongation condensates and provides a new perspective on how gene regulation is spatially organized within the nucleus.

Additionally, SFPQ and related proteins are associated with autism spectrum disorder and amyotrophic lateral sclerosis. Understanding abnormal expression of extra-long genes may offer insights into the mechanisms underlying neurodevelopmental and neurodegenerative disorders.