5′ValCAC tRNA fragment generated as part of a protective angiogenin response provides prognostic value in amyotrophic lateral sclerosis

• DOI: 10.1093/braincomms/fcaa138
• Publication Date: 2020-08-31T16:52:52Z
• Authors: Marion C Hogg; Megan Rayner; Sergej Susdalzew; Naser Monsefi; Martin Crivello; Ina Woods; Alexa Resler; Lisle Blackbourn; Paola Fabbrizio; Maria Chiara Trolese; Giovanni Nardo; Caterina Bendotti; Leonard H van den...; Michael A van Es; Jochen H M Prehn
• Keywords: Angiogenin; Stress granule

Abstract Loss-of-function mutations in the ribonuclease angiogenin are associated with amyotrophic lateral sclerosis. Angiogenin has been shown to cleave transfer RNAs during stress produce ‘transfer-derived stress-induced RNAs’. Stress-induced tRNA cleavage is preserved from single-celled organisms humans indicating it represents part of a highly conserved response. However, date, role sclerosis remains be fully elucidated. To this end, we performed small RNA sequencing on human astrocytoma cell line identify complete repertoire fragments generated by angiogenin. We found that only specific subset tRNAs cleaved and identified 5′ValCAC transfer-derived secreted neural cells. was quantified spinal cord serum SOD1G93A mouse models where significantly elevated at symptom onset correlating increased expression, imbalanced protein translation initiation factors slower disease progression. In patient samples, higher patients slow progression, interestingly, find hold prognostic value for patients. Here, report cleaves provide evidence as biomarker propose levels indicate an enhanced angiogenin-mediated response within motor neurons correlates survival. These data suggest previously reported beneficial effects mice may result fragment.