Fig. 5: RGTTCRA-tRFs decreased in the blood of DBS-treated patients with PD and in ribosomal fractions of depolarized neuroblastoma cells.

a, Blood was drawn from controls and patients with PD with and without DBS from the PPMI and Soreq datasets. b, RGTTCRA-tRF levels in control carriers of PD-related mutations (gray) and PD carriers of mutated LRRK2 or GBA genes (blue) with and without DBS (red and black outlines), n = 9, 11, 19. y: percentage of RGTTCRA-tRFs from total tRF counts (rhombuses indicate mean). PD versus Ctrl *P < 0.027, PD versus DBS #P < 0.095, one-way ANOVA. c, Ang levels in blood samples of controls and patients with PD before and after DBS treatment, from the Soreq dataset (GSE23676), colors as in b. Dashed lines connect pre-DBS and post-DBS samples of each patient (six Ctrl, seven PD). PD pre-DBS versus DBS *P < 0.019, one-way ANOVA. d, Small RNA-seq and ribosome-bound RNA-seq fractions of depolarized SHSY-5Y cells (GSE155727) conducted at resting, immediately after depolarization (Dep) and 2 h pDP. e, RGTTCRA-tRF (y axis) fractions in each of the cases described in d (x axis). Four biological replicates in each condition. Cytosolic small RNA: resting versus Dep *P < 0.01, resting versus 2 h pDP *P < 0.015, Dep versus 2 h pDP ***P < 0.0001; ribosome fraction: 2 h pDP versus resting *P < 0.015, 2 h pDP versus Dep *P < 0.0065; two-way ANOVA. f, Total and ribosome-bound fractions of RGTTCRA-tRFs (purple), MT-tRFs (green) and all other tRFs (gray) in whole cells (left) and ribosome-bound fractions (right). Columns: samples and black lines represent mean RGTTCRA-tRF or MT-tRF percentages in samples. Reduction in MT-tRF in cytosolic small RNA 2 h pDP, P < 0.0033, two-way ANOVA. Three samples with altered ratios of RGTTCRA-tRFs and MT-tRFs 2 h pDP in ribosomal fractions (compared to mean distribution in resting cells), *P < 0.022, **P < 0.006, *P < 0.024, chi-square, FDR. All box plots in this figure are defined so that the central line of the box plot represents the median; the lower and upper box bounds represent 0.25 and 0.75 quantiles; and lower and upper whisker bounds represent 0 and 1 quantiles.