What is it about?

We discovered the role of an RNA-binding protein, Quaking5 (Qki5), which generates the Motorneuron (MN) specific transcriptome profile, termed “MN-ness,” through the posttranscriptional network. Moreover, Qki5 contributes to the maintenance of motor neurons and its dysfunction is associated with MN vulnerability.

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Why is it important?

Many RNA-binding proteins (RBPs) are linked to the dysregulation of RNA metabolism in motor neuron diseases (MNDs). However, the specific molecular mechanisms underlying MN vulnerability have yet to be elucidated. We have attempted to explore the RBPs that define MN-ness and identified Qki5 as a MN-specific RBP among several types of neurons. We also revealed that Qki5-dependent RNA regulation plays a pivotal role in generating the MN-specific transcriptome through pre-messenger ribonucleic acid (mRNA) splicing for the several MN-disease relating pathways. We now believe that MNDs can be overcome by understanding the intrinsic weaknesses of motor neurons.

Perspectives

We focus on the physiological function of the motor neuron-specific RNA binding protein, Quaking5 (Qki5), in motor neurons. Also, this study points out the importance of Qki5 in the pathophysiology of motor neurons. In future studies, we would like to gain insights into the relationship Qki5 and human motor neuron diseases.

Yoshika Hayakawa-Yano
Keio Gijuku Daigaku

We have been focusing on the roles of cell type-specific RBPs to understand how they generate cell type-specific transcriptomes and function in the central nervous system since 2005. I hope this article provides the impacts on basic RNA biology and basis of potential therapeutic targets to several neurological diseases. Hitomi Yoshida rearranged our picture, which shows Qki5 (pink) and nELAVL (cyan) (below).

Masato Yano
Niigata Daigaku

Read the Original

This page is a summary of: Qki5 safeguards spinal motor neuron function by defining the motor neuron-specific transcriptome via pre-mRNA processing, Proceedings of the National Academy of Sciences, September 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2401531121.
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