A family of proteins involved in RNA degradation plays an unexpected role in transporting mRNAs out of the nucleus and directing them to neuronal dendrites for translation, report di Penta et al.

mRNAs encoding synaptic proteins are targeted to dendrites in the form of messenger ribonucleoprotein (mRNP) complexes. mRNA expression is silenced until the stimulation of synapses activates their translation into proteins that change synaptic strength, allowing neurons to record long-term memories and learning. But little is known about how and when mRNPs destined for dendrites are assembled.

Proteins involved in mRNA degradation would be last on a list of possible candidates for transporting mRNPs to synapses. But di Penta et al. had been studying one such degradation protein called LSm1 and found that in neurons the protein localized to dendrites—far away from the cell body where LSm proteins promote mRNA decay. The researchers' surprise and interest grew when they discovered that LSm1 was associated with mRNAs that localize to dendrites, and that these transcripts were not being degraded.

But, according to author Tilmann Achsel, the team was only convinced that LSm1 was involved in dendritic transport when they found that LSm1-mRNP complexes contained a cap-binding protein, indicating an intact 5′ end of the mRNA. This factor turned out to be the nuclear mRNA cap-binding protein CBP80, indicating that the LSm1-containing mRNP complexes had been assembled in the nucleus. The team showed that after nuclear export and transport to dendrites, the complexes delivered their mRNAs directly to the synapses for translation after synaptic stimulation.

Achsel says that the decision to transport mRNPs to dendrites is made in the nucleus when the complex is first assembled. Intriguingly, the LSm1-mRNP complex also localizes to the axons of spinal cord motor neurons and additionally contains a protein called SMN that is linked to spinal muscular atrophy. Achsel and colleagues are now interested in how this mRNP is involved in axonal development, and whether compromising its function results in disease.

di Penta
et al
J. Cell Biol.