The hidden SINEs of recovery" Repeat element RNAs integrate neuronal growth after injury"

You are cordially invited to a special seminar

of the Department of Physiology and Pharmacology and the

Department of Human Molecular Genetics and Biochemistry

By:

Eitan Erez Zehavi, PhD

"The hidden SINEs of recovery"

Repeat element RNAs integrate neuronal growth after injury

Neuronal growth and regeneration are regulated by specific gene transcription and translation programs that integrate mRNA localization, local protein synthesis, retrograde signaling and transcription factor (TF) activity. While the role of protein coding genes in these processes is well studied, that of regulatory RNAs is little understood. In a screen to identify RNA polyadenylation changes in mouse dorsal root ganglia (DRG) sensory neurons following sciatic nerve injury, we found the upregulation of polyadenylated B2-SINE repeat elements. Employing long-read paired-end RNA-seq and ATAC-seq analyses we pinpointed the upregulation to a subset of B2-SINE loci that undergo injury-induced chromatin accessible remodeling. This transcriptional upregulation was specific to injured peripheral sensory neurons and did not occur retinal ganglion cells following optic nerve crush. Importantly, expression of B2-SINE RNA in retinal and cortical neurons, whose intrinsic ability to regenerate is poorer than that of DRG neurons, significantly improved their regrowth after nerve injury. Hence, we termed this subset of injury-induced, DRG specific elements GI-SINE (growth-inducing B2-SINE). GI-SINEs are induced as discrete transcriptional units from the injury-activated and pro-regenerative ATF3 and other AP-1 TFs associated loci. GI-SINE RNA interacts with ribosomal proteins and nucleolin, an axon-growth-regulating RNA binding protein, to regulate translation in neuronal cytoplasm. Finally, antisense oligos against GI-SINEs perturb sensory neuron outgrowth and nucleolin-ribosome interactions. Thus, we identify a subfamily of transposable element RNAs that is integral in a signaling circuit regulating neuronal regrowth, suggesting similar elements can be utilized as regulated regenerative effectors in other physiological contexts.

The Seminar will take place on Thursday, December 25th, 10:15-11:00

At the Faculty of Medical & Health Sciences, Room 119