1. Rethinking Unconventional Translation in Neurodegeneration
- Author
-
Gao, Fen-Biao, Richter, Joel D, and Cleveland, Don W
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Neurodegenerative ,Genetics ,Neurosciences ,Animals ,Codon ,Initiator ,Frameshifting ,Ribosomal ,Humans ,Neurodegenerative Diseases ,Open Reading Frames ,Protein Biosynthesis ,Regulatory Sequences ,Ribonucleic Acid ,Trinucleotide Repeat Expansion ,ALS ,C9ORF72 ,dipeptide repeat proteins ,frontotemporal dementia ,near-cognate start codon ,repeat expansion ,translation ,upstream open reading frame ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
Eukaryotic translation is tightly regulated to ensure that protein production occurs at the right time and place. Recent studies on abnormal repeat proteins, especially in age-dependent neurodegenerative diseases caused by nucleotide repeat expansion, have highlighted or identified two forms of unconventional translation initiation: usage of AUG-like sites (near cognates) or repeat-associated non-AUG (RAN) translation. We discuss how repeat proteins may differ due to not just unconventional initiation, but also ribosomal frameshifting and/or imperfect repeat DNA replication, expansion, and repair, and we highlight how research on translation of repeats may uncover insights into the biology of translation and its contribution to disease.
- Published
- 2017