SNORD90 induces glutamatergic signaling following treatment with monoaminergic antidepressants
- McGill Group for Suicide Studies, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Canada
- Integrated Program in Neuroscience, McGill University, Canada
- Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Germany
- Department of Brain Sciences, Weizmann Institute of Science, Israel
- Department of Molecular Neuroscience, Weizmann Institute of Science, Israel
- Neuroscience Division, Douglas Research Centre, Canada
- Department of Psychiatry, McGill University, Canada
- Aix-Marseille Université, CNRS, INT, Institute Neuroscience Timone, France
- UMR 1253, iBrain, UFR Sciences et Techniques; Parc Grandmont, France
- Mood Disorders Research Unit, University of Ottawa Institute of Mental Health Research, Canada
- eBrain Lab, Simon Fraser University, Canada
- Department of Psychiatry and Behavioural Neurosciences, McMaster University, Canada
- Mood Disorders Program, St. Joseph’s Healthcare Hamilton, Canada
- Department of Psychiatry, University of British Columbia, Canada
- Departments of Psychiatry and Psychology, Queens University, Canada
- Department of Psychiatry, University Health Network, Krembil Research Institute, University of Toronto, Canada
- Centre for Addiction and Mental Health, Canada
- Department of Psychiatry, University of Michigan, United States
- Nova Scotia Health Authority, Canada
- Department of Psychiatry, Dalhousie University, Canada
- St Michael’s Hospital, Li Ka Shing Knowledge Institute, Centre for Depression and Suicide Studies, Canada
Figures
Figure 1 with 2 supplements
SNORD90 expression is associated with antidepressant treatment response.
(A) Two-way mixed multivariable ANOVA indicates a significant interaction between clinical response (responders/non-responders; between-factor) and treatment course (T0/T8; within factor). Nine snoRNAs displayed significant effects in the discovery cohort. Five out of the nine snoRNAs were replicated in replication cohort 1 with SNORD90 and SCARNA3 further replicated in replication cohort 2. (B) Log2 fold-change of the expression of SNORD90 before and after antidepressant treatment for all three clinical cohorts. SNORD90 displayed significantly increased expression after eight weeks of antidepressant treatment specifically in those who responded across all three clinical cohorts. See Figure 1—figure supplement 1A for SCARNA3 expression (C) SNORD90 expression in human post-mortem ACC. Using toxicology screens, each sample was separated into the following groups: MDD with presence of antidepressants (MDD +AD; n=7), MDD with presence of non-antidepressant drugs (MDD +nonAD drugs; n=18), MDD with negative toxicology screen (MDD; n=8), controls with non-antidepressant drugs (control +nonAD drugs; n=15), and controls with negative toxicology screens (control; n=26). No control samples were positive for antidepressant drugs. (D) Snord90 expression in the ACC of mice that underwent unpredictable chronic mild stress (UCMS) and fluoxetine (flx) administration (UCMS + flx, n=5; UCMS, n=7; control +flx, n=6; control, n=5). (E) SNORD90 expression in human neuronal cultures exposed to various psychotropic drugs (n=4 per group). All bar plots represent the mean with individual data points as dots. Error bars represent S.E.M. One-way ANOVA with Bonferroni post-hoc (unless otherwise indicated on the graph). *p<0.05, **p<0.01, ***p<0.001.
Figure 1—figure supplement 1
SCARNA3 expression in human clincial cohorts and SNORD90 expression in neuronal and non-neuronal cell types from human post-mortem ACC.
(A) Log2 fold-change of the expression of SCARNA3 before and after antidepressant treatment for all three clinical cohorts. SCARNA3 displayed inconsistent expression across the three clinical cohorts after eight weeks of antidepressant treatment. (B) Fluorescence-activated nuclei sorting (FANS) sorted nuclei, collected from human port-mortem ACC samples, into NeuN+ (neuronal) or NeuN- (non-neuronal) cell types. SNORD90 expression in NeuN+ (left) and NeuN-(right). Using toxicology screens, each sample was separated into the following groups: MDD with presence of antidepressants (MDD +AD; n=5), MDD with presence of non-antidepressant drugs (MDD +nonAD drugs; n=9), MDD with negative toxicology screen (MDD; n=4), controls with non-antidepressant drugs (control +nonAD drugs; n=13), and controls with negative toxicology screens (control; n=16). No control samples were positive for antidepressant drugs. All bar plots represent the mean with individual data points as dots. Error bars represent S.E.M. Two-way mixed multivariable ANOVA (A), One-way ANOVA (B) with Bonferroni post-hoc. *p<0.05.
Figure 1—figure supplement 2
NRG3 expression is negatively associated with SNORD90 expression.
(A) NRG3 expression in human post-mortem ACC. Using toxicology screens, each sample was separated into the following groups: MDD with presence of antidepressants (MDD +AD; n=10), MDD with presence of non-antidepressant drugs (MDD +nonAD drugs; n=16), MDD with negative toxicology screen (MDD; n=8), controls with non-antidepressant drugs (control +nonAD drugs; n=12), and controls with negative toxicology screens (control; n=25). No control samples were positive for antidepressant drugs. (B) Nrg3 expression in the ACC of mice that underwent unpredictable chronic mild stress (UCMS) and fluoxetine (flx) administration (UCMS +flx, n=5; UCMS, n=7; control +flx, n=6; control, n=5). (C) NRG3 expression in human neuronal cultures exposed to various psychotropic drugs (n=4 per group). (D–F) Correlation between SNORD90/Snord90 and NRG3/Nrg3 within each of the experiments detailed in (A–C). SNORD90/Snord90 and NRG3/Nrg3 displayed a significant negative correlation within each experiment. (G–I) SNORD90/Snord90 (red) and NRG3/Nrg3 (black) fold change in relation to control conditions plotted together within each experiment detailed in (A–C). SNORD90/Snord90 and NRG3/Nrg3 displayed the most opposing direction of expression in groups exposed to antidepressants in each of the experiments. All bar plots represent the mean with individual data points as dots. Error bars represent S.E.M. One-way ANOVA with Bonferroni post-hoc (A–C) Pearson correlation (D–F). Two-way mixed ANOVA with Bonferroni post-hoc (G–I). *p<0.05, **p<0.01.
Figure 2
Snord90 over-expression in mouse Cg1/2 induces anxiolytic and anti depressive-like behaviors.
(A) Timeline of experimental procedure with time (weeks) in relation to behavioral testing. Surgery for viral injection was performed followed by 3 weeks of recovery before behavioral testing (left). Coronal diagram of the mouse brain representing viral injection of Snord90 expression vector (Snord90 O.E., n=18) or scramble control expression vector (scramble O.E., n=18) into Cg1/2 (mouse equivalent to human ACC) (center). Representative images of GFP expression indicating site specific expression of each construct (right). (B) The open field test showing total distance traveled in meters. (C) The elevated plus maze test with total time spent in the closed arms, center, and open arms of the plus maze. (D) The splash test (10% sucrose solution) with total grooming time. (E) The tail suspension test with total struggling time. (F) Emotionality z-score integrating the elevated plus maze, splash test, and tail suspension test. All bar plots represent the mean with individual animals as dots. Error bars represent S.E.M. Student’s two-tailed t-test. *p<0.05, **p<0.01.
Figure 3 with 1 supplement
SNORD90 down-regulates NRG3.
(A) Full sequence of mature SNORD90 transcript with highlighted regions labeled predicted binding site (B.S.) 1 and predicted B.S. 2, which are predicted to bind to NRG3. Schematic representation of NRG3 pre-mRNA transcript indicating regions on NRG3 where SNORD90 is predicted to bind. The color of the bracket corresponds to predicted B.S.-1 or predicted B.S.-2. (red nucleotide indicates mismatch, orange nucleotide indicates G-T wabble pair). (B) Expression of SNORD90 (left) and NRG3 (right) in human NPCs after transfection with SNORD90 expression vector (SNORD90 O.E., n=6), seed scramble expression vector (seed scramble O.E., n=6), and full scramble expression vector (full scramble O.E., n=6). Non-transfected NPCs under normal culture conditions as control (n=6) (C) Expression of SNORD90 (left) and NRG3 (right) after transfecting human NPCs with an antisense oligonucleotides (ASO) designed to knock-down SNORD90 (SNORD90 K.D., n=6) or scrambled ASO (scramble K.D., n=6). Non-transfected NPCs under normal culture conditions as control (n=6). (D) Schematic representation of co-transfection of SNORD90 over-expression vector without target blockers (top) and with target blockers (bottom). Target blockers designed to bind to regions on pre-NRG3 where SNORD90 is predicted to bind, consequently blocking SNORD90 from interacting with those regions on NRG3 (bottom). (E) NRG3 expression following SNORD90 expression vector co-transfected with a scrambled blocker (+scramble blocker, n=6), target blockers one site at a time (+Blocker 1, n=6;+Blocker 2, n=6, and +Blocker 3, n=6), or all three blockers simultaneously (+Blocker1-to-3, n=6). Non-transfected NPCs under normal culture conditions as control (n=6). All bar plots represent the mean with individual data points as dots. Error bars represent S.E.M. One-way ANOVA with Bonferroni post-hoc. **p<0.01, ****p<0.0001.
Figure 3—figure supplement 1
SNORD90 over-expression and knock-down in human NPC culture.
(A) Sequences of each primary transcript used for over-expression experiment in human NPC culture. SNORD90 O.E. (top), seed scramble O.E. (middle), and full scramble O.E. (bottom). Red indicates scrambled sequence and black indicates wild-type sequence. Yellow highlight sequence indicates where forward and reverse primers bind for qPCR quantification. Over-expression of SNORD90 WT transcript and seed scramble will be detected by our primers however full scramble will not. (B) Image of human NPC culture 48 hr post-transfection. White indicates the expression of GFP to confirm successful transfection. (C) Schematic representation of expression vectors used to over-expression primary transcripts (A) in human NPC culture (B). (D) Western blot quantification of NRG3 protein levels following transfection of SNORD90 (SNORD90 O.E., n=5), or full scramble (full scramble O.E., n=5) expression vectors in human NPC culture. Non-transfected NPCs under normal culture conditions as control (n=5). Samples were equally distributed between two separate gels and randomly assigned a well within each gel (right). (E–J) Expression of ENG (E), ST6GALNAC3 (F), ARHGAP29 (G), LDLRAD4 (H), EXOC6B (I), and SPOCK3 (J) in human NPCs after transfection with SNORD90 expression vector (SNORD90 O.E., n=6), seed scramble expression vector (seed scramble O.E., n=6), and full scramble expression vector (full scramble O.E., n=6). Non-transfected NPCs under normal culture conditions as control (n=6). (K) Schematic diagram indicating where each antisense oligonucleotides (ASO) is designed to target and cleave SNORD90. (L) Each of the four ASOs (ASO1, n=6; ASO2, n=6; ASO3, n=6; ASO4, n=6) were separably transfected into human NPCs to determine which achieved the most significant knock-down of SNORD90 expression. Scrambled ASO (scramble, n=6) and non-transfected NPCs under normal culture conditions as control (control, n=6). ASO4 was selected (subsequently referred to as SNORD90 K.D.). (M–R) Expression of ENG (M), ST6GALNAC3 (N), ARHGAP29 (O), LDLRAD4 (P), EXOC6B (Q), and SPOCK3 (R) after transfecting human NPCs with an ASO designed to knock-down SNORD90 (SNORD90 K.D., n=6) or scrambled ASO (scramble K.D., n=6). Non-transfected NPCs under normal culture conditions as control (n=6). (S) Same as (E–J) but for pre-NRG3 expression. (T) Same as (M–R) but for pre-NRG3 expression. (U) Expression of pre-NRG3 following SNORD90 expression vector was co-transfected with scrambled blocker (+scramble blocker, n=6), target blockers one site at a time (+Blocker 1, n=6;+Blocker 2, n=6, and +Blocker 3, n=6), or all three sites together (+Blocker1-to-3, n=6). Non-transfected NPCs under normal culture conditions as control (n=6). All bar plots represent the mean with individual data points as dots. Error bars represent S.E.M. One-way ANOVA with Bonferroni post-hoc. *p<0.05, **p<0.01, ***p<0.001.
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Figure 3—figure supplement 1—source data 1
Original uncropped western blots for NRG3 and GAPDH found in Figure 3—figure supplement 1D.
- https://cdn.elifesciences.org/articles/85316/elife-85316-fig3-figsupp1-data1-v1.zip
Figure 4 with 1 supplement
SNORD90 is a guide RNA for RBM15B and increases m6A abundance on NRG3.
(A) Presence of SNORD90 (left) and canonical snoRNA, SNORD44, (right) in RBM15B-IP (n=6) and fibrillarin-IP (n=6) fractions. SNORD90 displayed higher levels in association with RBM15B as compared to fibrillarin, whereas the canonical snoRNA control displayed higher association to fibrillarin and almost no association with RBM15B. Black dots are IgG negative control (n=3) (B) Presence of SNORD90 in RBM15B-IP (left) and fibrillarin-IP (right) following transfection of SNORD90 (SNORD90 O.E.; n=6) or scramble (scramble O.E.; n=6) expression vectors in human NPC culture. SNORD90 O.E. increased SNORD90 detection after RBM15B-IP whereas detection of SNORD90 in fibrillarin-IP remained unchanged, suggesting that SNORD90 has preferential binding to RBM15B as compared to fibrillarin. Black dots indicate IgG negative control (n=3) (C) Abundance of m6A modifications on pre-NRG3 following transfection of SNORD90 (SNORD90 O.E.; n=6), seed scramble (seed scramble O.E.; n=6), and full scramble (full scramble O.E.; n=6) expression vectors in human NPC culture; non-transfected NPCs under normal culture conditions as controls (control; n=6) (D) Schematic diagram of SNORD90’s role in guiding m6A-methyltransferase complex onto pre-NRG3 in the nucleus. M6A modifications deposited onto pre-NRG3 are retained on mature NRG3. (E) Same as (C) but for mature NRG3. (F) Correlation between m6A abundance and RNA expression for pre-NRG3 (top) and mature NRG3 (bottom). Significant correlation only observed for mature NRG3. (G–H) Human NPCs were first transfected with dsiRNA to knock-down RBM15B (siRBM15B) or scrambled control (siControl) followed by transfection with SNORD90 expression vector (siRBM15B+SNORD90 O.E., n=5; siControl +SNORD90 O.E., n=6). Non-transfected NPCs under normal culture conditions as controls (control, n=6). M6A abundance (top) and RNA expression (bottom) were measured for pre-NRG3 (G) and mature NRG3 (H). (I) Correlation between m6A abundance and RNA expression for pre-NRG3 (top) and mature NRG3 (bottom). Correlation data from (G–H). Significant correlation only observed for mature NRG3. All bar plots represent the mean with individual data points as dots. Error bars represent S.E.M. Student’s two-tailed t test (A–B). Pearson correlation (F) & (I).One-way ANOVA with Bonferroni post-hoc (C & E & G-H). **p<0.01, ***p<0.001.
Figure 4—figure supplement 1
m6A abundance and RBM15B knock-down in human NPC culture.
(A–B) Abundance of m6A on pre-NRG3 (A) and NRG3 (B) following co-transfection of SNORD90 expression vector co-transfected with a scrambled blocker (+scramble blocker, n=6), or target blockers targeting all three sites simultaneously (+Blocker1-to-3, n=6). Non-transfected NPCs under normal culture conditions as control (n=6). (C) Western blot validation of dsiRNA designed to target RBM15B. Human NPCs were transfected with dsiRNAs targeting RBM15B (siRBM15B, n=3), or scrambled dsiRNA control (siControl, n=3). Non-transfected NPCs under normal culture conditions as control (WT, n=3). (D) RBM15B mRNA expression assessed in the same samples presented in Figure 4G–H to confirm RBM15B knock-down in final experiment. All bar plots represent the mean with individual data points as dots. Error bars represent S.E.M. One-way ANOVA with Bonferroni post-hoc. *p<0.05, **p<0.01, ***p<0.001., ****p<0.0001.
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Figure 4—figure supplement 1—source data 1
Original uncropped western blots for RBM15B and GAPDH found in Figure 4—figure supplement 1C.
- https://cdn.elifesciences.org/articles/85316/elife-85316-fig4-figsupp1-data1-v1.zip
Figure 5 with 1 supplement
SNORD90-induced m6A on NRG3 is recognized by YTHDF2.
(A) NRG3 expression in human NPCs transfected with dsiRNA to knock-down the m6A readers YTHDF1 (siDF1), YTHDF2 (siDF2), YTHDF3 (siDF3), YTHDC1 (siDC1), and YTHDC2 (siDC2) or a scramble control (siControl) followed by transfection with SNORD90 expression vector (siDF1 +SNORD90 O.E., n=6; siDF2 +SNORD90 O.E., n=5; siDF3 +SNORD90 O.E., n=6; siDC1 +SNORD90 O.E., n=6; siDC2 +SNORD90 O.E., n=6, siControl +SNORD90 O.E., n=6). Non-transfected NPCs under normal culture conditions as controls (control, n=6). YTHDF2 knock-down showed the most robust ability to blunt SNORD90’s downregulatory effect on NRG3 suggesting it plays the largest role in recognizing m6A abundance on NRG3. (B) Schematic overview of SNORD90’s regulation of NRG3 expression. SNORD90 interacts with m6A methyltransferase complex in the nucleus and guides this complex onto pre-NRG3 increasing m6A abundance. The increase in m6A abundance is maintained throughout pre-mRNA maturation (supposedly this increase in m6A is being deposited onto exonic regions) is not recognized until NRG3 reaches the cytoplasm where it undergoes YTHDF2 mediated RNA decay. Bar plot represent the mean with individual data points as dots. Error bars represent S.E.M. One-way ANOVA with Bonferroni post-hoc. *p<0.05, **p<0.01.
Figure 5—figure supplement 1
m6A-reader knock-down in human NPC culture.
(A–E) Western blot validation of dsiRNA designed to target YTHDF1 (A), YTHDF2 (B), YTHDF3 (C), YTHDC1 (D), and YTHDC2 (E). Human NPCs were transfected with dsiRNAs targeting YTHDF1 (siDF1, n=3), YTHDF2 (siDF2, n=3), YTHDF3 (siDF3, n=3), YTHDC1 (siDC1, n=3), YTHDC2 (siDC2, n=3), or scrambled dsiRNA control (siControl, n=3). Non-transfected NPCs under normal culture conditions as control (WT, n=3). (F–J) YTHDF1 (F), YTHDF2 (G), YTHDF3 (H), YTHDC1 (I), and YTHDC2 (J) mRNA expression assessed in the same samples presented in Figure 5A &Figure 5-figure supplement 1K to confirm each m6A-reader knock-down in final experiment. (K) Pre-NRG3 expression in human NPCs transfected with dsiRNA to knock-down the m6A readers YTHDF1 (siDF1), YTHDF2 (siDF2), YTHDF3 (siDF3), YTHDC1 (siDC1), and YTHDC2 (siDC2) or a scramble control (siControl) followed by transfection with SNORD90 expression vector (siDF1 +SNORD90 O.E., n=6; siDF2 +SNORD90 O.E., n=5; siDF3 +SNORD90 O.E., n=6; siDC1 +SNORD90 O.E., n=6; siDC2 +SNORD90 O.E., n=6, siControl +SNORD90 O.E., n=6). Non-transfected NPCs under normal culture conditions as controls (control, n=6). All bar plots represent the mean with individual data points as dots. Error bars represent S.E.M. One-way ANOVA with Bonferroni post-hoc. *p<0.05, **p<0.01, ***p<0.001., ****p<0.0001.
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Figure 5—figure supplement 1—source data 1
Original uncropped western blots for YTHDF1 and GAPDH found in Figure 5—figure supplement 1A.
- https://cdn.elifesciences.org/articles/85316/elife-85316-fig5-figsupp1-data1-v1.zip
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Figure 5—figure supplement 1—source data 2
Original uncropped western blots for YTHDF2 and GAPDH found in Figure 5—figure supplement 1B.
- https://cdn.elifesciences.org/articles/85316/elife-85316-fig5-figsupp1-data2-v1.zip
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Figure 5—figure supplement 1—source data 3
Original uncropped western blots for YTHDF3 and GAPDH found in Figure 5—figure supplement 1C.
- https://cdn.elifesciences.org/articles/85316/elife-85316-fig5-figsupp1-data3-v1.zip
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Figure 5—figure supplement 1—source data 4
Original uncropped western blots for YTHDC1 and GAPDH found in Figure 5—figure supplement 1D.
- https://cdn.elifesciences.org/articles/85316/elife-85316-fig5-figsupp1-data4-v1.zip
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Figure 5—figure supplement 1—source data 5
Original uncropped western blots for YTHDC2 and GAPDH found in Figure 5—figure supplement 1E.
- https://cdn.elifesciences.org/articles/85316/elife-85316-fig5-figsupp1-data5-v1.zip
Figure 6 with 1 supplement
Snord90 induced down-regulation of Nrg3 increases glutamatergic neurotransmission.
(A) Full sequence of mature mouse Snord90 transcript with highlighted region predicted to bind to mouse Nrg3. Schematic representation of Nrg3 pre-mRNA transcript indicating regions on Nrg3 where Snord90 is predicted to bind (red nucleotide indicates mismatch, orange nucleotide indicates G-T wabble pair). (B) Viral injection of Snord90 expression vector (Snord90 O.E., n=9) or scramble control expression vector (scramble O.E., n=9) into Cg1/2 followed by qPCR confirmation Snord90 over-expression (left) and subsequent Nrg3 down-regulation (right). (C–E) Whole-cell patch-clamp recordings in Cg1/2 acute brain slices from mice. sEPSCs frequency (C) and sEPSCs amplitude (D) with cumulative probability plots (Snord90 O.E., n=19 neurons from 8 animals; scramble O.E., n=12 neurons from 3 animals) (E) Representative trace recording of sEPSCs in Cg1/2 pyramidal neurons. All bar plots represent the mean with individual data points as dots. Error bars represent S.E.M. Student’s two-tailed T-test. *p<0.05, **p<0.01, ****p<0.0001.
Figure 6—figure supplement 1
A schematic diagram depicting the working model proposed by Wang et al., 2018 showing NRG3’s role in regulating glutamatergic neurotransmission.
NRG3 interacts with syntaxin, disrupting SNARE complex formation in the presynaptic terminal which in turn inhibits vesicle docking disrupting glutamate release.
Additional files
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Supplementary file 1
Summary statistics for small RNA sequencing analysis in human clinical discovery cohort.
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp1-v1.xlsx
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Supplementary file 2
Summary statistics for small RNA sequencing analysis in human clinical replication 1 cohort.
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp2-v1.xlsx
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Supplementary file 3
Summary statistics for small RNA sequencing analysis in human clinical replication 2 cohort.
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp3-v1.xlsx
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Supplementary file 4
Sequences for over-expression.
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp4-v1.xlsx
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Supplementary file 5
SNORD90 BLAST target prediction.
Genes highlighted in green were selected for wet lab confirmation.
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp5-v1.xlsx
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Supplementary file 6
SNORD90 PLEXY target prediction (whole genome).
Transcripts highlighted in green were selected for wet lab confirmation. Target sites in bold are sites used for target blocker design. (a) Parenthesis indicates complimentary base match between SNORD90 and target site. Dot indicates mismatch. (b) Sequence of the target site and site on SNORD90. Match column indicates sequence complementarity or mismatch shown here. m: 2’-O-ribose methylation site.
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp6-v1.xlsx
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Supplementary file 7
SNORD90 PLEXY target prediction (NRG3 targeted).
Target sites in bold are sites used for target blocker design. (a) Parenthesis indicates complimentary base match between SNORD90 and target site. Dot indicates mismatch. (b) Sequence of the target site and site on SNORD90. Match column indicates sequence complementarity or mismatch shown here. m: 2’-O-ribose methylation site.
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp7-v1.xlsx
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Supplementary file 8
ASO sequences.
m: 2’-O-methyl base; *: Phosphorothioate bond
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp8-v1.xlsx
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Supplementary file 9
Target blocker sequences.
2MOEr: 2’-O-methoxyethyl RNA base; /*/: Phosphorothioate bond
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp9-v1.xlsx
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Supplementary file 10
RBP motif on SNORD90.
(a) A value of 0 and 1 is assigned for each putative RBP motif identified on SNORD90 where 1 is the canonical motif. (b) Corresponds to the probability of the 7-mer region being structurally unpaired (lower score corresponds to lower probability)
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp10-v1.xlsx
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Supplementary file 11
Snord90 PLEXY target prediction (whole genome).
Target sites highlighted in green display the highest probability for Snord90 interaction on Nrg3 (a) Parenthesis indicates complimentary base match between SNORD90 and target site. Dot indicates mismatch. (b) Sequence of the target site and site on SNORD90. Match column indicates sequence complementarity or mismatch shown here. m: 2’-O-ribose methylation site.
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp11-v1.xlsx
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Supplementary file 12
Primer sequences.
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp12-v1.xlsx
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Supplementary file 13
DsiRNA sequences.
- https://cdn.elifesciences.org/articles/85316/elife-85316-supp13-v1.xlsx
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MDAR checklist
- https://cdn.elifesciences.org/articles/85316/elife-85316-mdarchecklist1-v1.pdf
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SNORD90 induces glutamatergic signaling following treatment with monoaminergic antidepressants
eLife 12:e85316.
https://doi.org/10.7554/eLife.85316
