TY - JOUR
T1 - Cerebrospinal fluid and blood profiles of transfer RNA fragments show age, sex, and Parkinson's disease-related changes
AU - Paldor, Iddo
AU - Madrer, Nimrod
AU - Vaknine Treidel, Shani
AU - Shulman, Dana
AU - Greenberg, David S.
AU - Soreq, Hermona
N1 - Publisher Copyright:
© 2022 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.
PY - 2023/3
Y1 - 2023/3
N2 - Transfer RNA fragments (tRFs) have recently been shown to be an important family of small regulatory RNAs with diverse functions. Recent reports have revealed modified tRF blood levels in a number of nervous system conditions including epilepsy, ischemic stroke, and neurodegenerative diseases, but little is known about tRF levels in the cerebrospinal fluid (CSF). To address this issue, we studied age, sex, and Parkinson's disease (PD) effects on the distributions of tRFs in the CSF and blood data of healthy controls and PD patients from the NIH and the Parkinson's Progression Markers Initiative (PPMI) small RNA-seq datasets. We discovered that long tRFs are expressed in higher levels in the CSF than in the blood. Furthermore, the CSF showed a pronounced age-associated decline in the level of tRFs cleaved from the 3′-end and anti-codon loop of the parental tRNA (3’-tRFs, i-tRFs), and more pronounced profile differences than the blood profiles between the sexes. In comparison, we observed moderate age-related elevation of blood 3’-tRF levels. In addition, distinct sets of tRFs in the CSF and in the blood segregated PD patients from controls. Finally, we found enrichment of tRFs predicted to target cholinergic mRNAs (Cholino-tRFs) among mitochondrial-originated tRFs, raising the possibility that the neurodegeneration-related mitochondrial impairment in PD patients may lead to deregulation of their cholinergic tone. Our findings demonstrate that the CSF and blood tRF profiles are distinct and that the CSF tRF profiles are modified in a sex-, age-, and disease-related manner, suggesting that they reflect the inter-individual cerebral differences and calling for incorporating this important subset of small RNA regulators into future studies. (Figure presented.)
AB - Transfer RNA fragments (tRFs) have recently been shown to be an important family of small regulatory RNAs with diverse functions. Recent reports have revealed modified tRF blood levels in a number of nervous system conditions including epilepsy, ischemic stroke, and neurodegenerative diseases, but little is known about tRF levels in the cerebrospinal fluid (CSF). To address this issue, we studied age, sex, and Parkinson's disease (PD) effects on the distributions of tRFs in the CSF and blood data of healthy controls and PD patients from the NIH and the Parkinson's Progression Markers Initiative (PPMI) small RNA-seq datasets. We discovered that long tRFs are expressed in higher levels in the CSF than in the blood. Furthermore, the CSF showed a pronounced age-associated decline in the level of tRFs cleaved from the 3′-end and anti-codon loop of the parental tRNA (3’-tRFs, i-tRFs), and more pronounced profile differences than the blood profiles between the sexes. In comparison, we observed moderate age-related elevation of blood 3’-tRF levels. In addition, distinct sets of tRFs in the CSF and in the blood segregated PD patients from controls. Finally, we found enrichment of tRFs predicted to target cholinergic mRNAs (Cholino-tRFs) among mitochondrial-originated tRFs, raising the possibility that the neurodegeneration-related mitochondrial impairment in PD patients may lead to deregulation of their cholinergic tone. Our findings demonstrate that the CSF and blood tRF profiles are distinct and that the CSF tRF profiles are modified in a sex-, age-, and disease-related manner, suggesting that they reflect the inter-individual cerebral differences and calling for incorporating this important subset of small RNA regulators into future studies. (Figure presented.)
UR - http://www.scopus.com/inward/record.url?scp=85142501370&partnerID=8YFLogxK
U2 - 10.1111/jnc.15723
DO - 10.1111/jnc.15723
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C2 - 36354307
AN - SCOPUS:85142501370
SN - 0022-3042
VL - 164
SP - 671
EP - 683
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 5
ER -