Axonal #TDP43 is a thing!
Proud to share our recent review written together with brilliant Topaz Altman and Perlson lab. We discuss the known and also the postulated functions of axonal and synaptic TDP43, and how these may relate to its peripheral toxicity in #ALS

Pleased to share our recent publication 'Multiple Copies of #microRNA Binding Sites in Long 3'UTR Variants Regulate Axonal Translation' achieved in a unique collaboration between Perlson lab and lab of Noam Shomron. More details in thread. #Axons #RNA

mdpi.com/2073-4409/12/2…

Here's an excellent review recently put out by the Perlson lab (Perlson lab, Ariel Ionescu, Topaz Altman) about axonal functions of TDP-43 and neuromuscular junction dysfunction in ALS. #endALS

…arneurodegeneration.biomedcentral.com/articles/10.11…

New publication for our ALS Review Series Collection!

'Looking for answers far away from the soma—the (un)known #axonal functions of TDP-43, and their contribution to early NMJ disruption in #ALS '

Ariel Ionescu Topaz Altman Perlson lab TAU Faculty of Medical & Health Sciences

bit.ly/3OH8Brs

. 🌓mac⁷ RPWP Cindy Bin Szabó Mihály Máté HERODOTO VishvaMohan Rathinam vi | need GA moots ; medyo IA EntID Ariel Ionescu Tim Rossiter 𝓡𝓪𝓷𝓭𝓸𝓶 josh Hossam Elheta Del Luis Mustafa Akkol Xavier Champion BlessMe mr nduks Pete Marfatia Bruninha bb📖🔥🌵

Ariel Ionescu Perlson lab Noam Shomron 👏🏽👏🏽👏🏽

Congrats 🎉

Axons require a strict spatiotemporal control over their proteome. This has been shown to be achieved in part by local translation of mRNAs in axons and synapses, which is dependent on the active distribution of these mRNAs into axons through unique motifs in their 3'UTRs.

Ariel Ionescu Topaz Altman Perlson lab Wonderful as usual! Great team work!

I am grateful to Luba Farberov, my co-author in this work for this fruitful collaboration. 🙏🙏🙏

Further, we validate that indeed the longer KIF5B 3'UTR variant leads to a slower translation rate compared with the short-soma variant, and specifically reveal that this occurs due to the multiplicity of miR-129-5p sites.

Specifically, we report that miR-129-5p targets many of these axonal enriched variants via multiple binding sites. We show that Kinesin-1 heavy chain (KIF5B) mRNA has one of the longest 3'UTRs in axons vs. soma, which has 3 miR-129-5p binding sites vs. only 1 in soma variants.

Looking in axonal and soma RNA-seq data we couldn’t detect variations in target-site type between soma and axonal transcripts. We did however find that axonal mRNA variants carry longer 3’UTRs that contain multiple miRNA binding-site repeats for neuronal miRNAs.

Altogether, we suggest a new mechanism for the role and function of long 3'UTR mRNA variants in axons which could regulate their translation in space and time via their increased susceptibility to miRNA. For more details, I encourage you to check out the full article.

Here we used a FRAP assay to first monitor the effect of different miRNA seed to target complementation variations over the rate of dGFP translation in HEK cells, and revealed that these function as fine tuners of translation rather than being complete silencers.

Yet, the mechanisms that regulate the local transcriptome and translation in axons are largely unknown. miRNA are master regulators of protein expression that target transcripts mostly by binding of their 'seed' sequence to a complementary target site in the 3'UTR of mRNAs.

Ariel Ionescu Topaz Altman Perlson lab Congrats!

Ariel Ionescu Topaz Altman Perlson lab Congratulations to both of you Ariel Ionescu and Topaz Altman 🍾

Molecular Neurodegeneration Ariel Ionescu Topaz Altman Perlson lab TAU Faculty of Medical & Health Sciences Congratulations, Topaz, Ariel and Eran! On my reading list.