Ribosome traffic jam in neurodegeneration: decoding hurdles in Huntington disease
Authors:Srinivasa Subramaniam1
1 The Scripps Research Institute, Department of Neuroscience, Jupiter, FL, USA.
Keywords:
jamming, translocation, codon pause, striatum, brain disorder, mitochondria, occupancy.
Corresponding Author(s):
Conflict of interest statement:
The author declares no competing interests.
Please cite this article as:
Srinivasa Subramaniam (2021). Ribosome traffic jam in neurodegeneration: decoding hurdles in Huntington disease. Cell Stress 5(6): 86-88. doi: 10.15698/cst2021.06.251
© 2021 Subramaniam. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
A ribosome typically moves at a particular rate on a given mRNA transcript to decode the nucleic acid information required to synthesize proteins. The speed and directionality of the ribosome movements during mRNA translation are determined by the mRNA sequence and structure and by various decoding factors. However, the molecular mechanisms of this remarkable movement during protein synthesis, or its relevance in brain disorders, remain unknown. Recent studies have indicated that defects in protein synthesis occur in various neurodegenerative diseases, but the mechanistic details are unclear. This is a major problem because identifying the factors that determine protein synthesis defects may offer new avenues for developing therapeutic remedies for currently incurable diseases like neurodegenerative disorders. Based on our recent study (Eshraghi et al., Nat Commun 12(1):1461; doi: 10.1038/s41467-021-21637-y), this short commentary will review the mechanistic understanding of Huntingtin (HTT)-mediated ribosome stalling indicating that central defects in protein synthesis in Huntington disease (HD) are orchestrated by jamming of ribosomes on mRNA transcripts.