Funded Research Projects


Analysis of mRNA transport and local protein syntheses in axons of SMA motor neurons

Principal investigator(s):
Dr. Claudia Fallini
Emory University, USA
Grant Type:
Operating Grant
Start Year:
2 years
Call number:


Dr. Claudia Fallini

Q. Why are motor neurons specifically vulnerable to SMN deficiency?

A. Because of its special interaction with RNA binding proteins in the axon of nerves, loss of SMN may lead to failure to transport specific mRNAs to the end of nerves.

What were the researchers aiming to do?

In an attempt to identify why motor neurons are selectively vulnerable to low levels of SMN protein, Dr.  Fallini looked at defects in the transport and local translation of mRNAs (protein codes) in SMN-deficient motor neurons. She also looked at the association of SMN with several RNA binding proteins in the motor axons. She found defects in the axonal localization of a sequence called poly mRNA in motor neurons lacking SMN protein. This sequence promotes mRNA export from the nucleus, translation and protects it from degradation. She also demonstrated that SMN protein is needed for the efficient delivery of mRNAs to the motor axon.

What did their research show?

Dr. Fallini went on to characterise the SMN interaction with two well-known mRNA-building proteins involved with neuronal development and plasticity and cell movement respectively. She demonstrated that SMN interacts with these neurons axons and that this interaction depends on a particular domain. A mutation in this domain, known to cause SMA, impaired the interaction with one of them, but did not affect SMN axonal localisation or self-association. Importantly, she showed that the localization of both mRNA-binding proteins in the axon of motor neurons depends on SMN levels. Indeed, both protein levels were significantly reduced in the axons of motor neurons upon SMN knock down. This research supports the hypothesis that SMN has a role in motor neurons to help the assembly of protein complexes, allowing thier transport along the axon and the delivery of mRNA to the neuro-muscular junction (NMJ).