Functionally Clustered mRNAs Are Distinctly Enriched at Cortical Astroglial Processes and Are Preferentially Affected by FMRP Deficiency

Mature protoplasmic astroglia in the mammalian CNS uniquely possess a large number of fine processes that have been considered primary sites to mediate astroglia to neuron synaptic signaling. However, localized mechanisms for regulating interactions between astroglial processes and synapses, especially for regulating the expression of functional surface proteins at these fine processes, are largely unknown. Previously, we showed that the loss of the RNA binding protein FMRP in astroglia disrupts astroglial mGluR5 sig-naling and reduces expression of the major astroglial glutamate transporter GLT1 and glutamate uptake in the cortex of Fmr1 con-ditional deletion mice. In the current study, by examining ribosome localization using electron microscopy and identifying mRNAs enriched at cortical astroglial processes using synaptoneurosome/translating ribosome affinity purification and RNA-Seq in WT and FMRP-deficient male mice, our results reveal interesting localization-dependent functional clusters of mRNAs at astroglial processes. We further showed that the lack of FMRP preferentially alters the subcellular localization and expression of process-localized mRNAs. Together, we defined the role of FMRP in altering mRNA localization and expression at astroglial processes at the post-natal development (P30-P40) and provided new candidate mRNAs that are potentially regulated by FMRP in cortical astroglia.

Automated summary

This study investigates the role of FMRP in astroglial processes and reveals that the loss of FMRP affects mRNA localization and expression. These findings provide new insights into the interactions and signaling mechanisms between astroglial processes and synapses.