A MicroRNA Feedback Circuit in Midbrain Dopamine Neurons
Open accessAbstract
MicroRNAs (miRNAs) are evolutionarily conserved, 18- to 25-nucleotide, non–protein coding transcripts that posttranscriptionally regulate gene expression during development. miRNAs also occur in postmitotic cells, such as neurons in the mammalian central nervous system, but their function is less well characterized. We investigated the role of miRNAs in mammalian midbrain dopaminergic neurons (DNs). We identified a miRNA, miR-133b, that is specifically expressed in midbrain DNs and is deficient in midbrain tissue from patients with Parkinson's disease. miR-133b regulates the maturation and function of midbrain DNs within a negative feedback circuit that includes the paired-like homeodomain transcription factor Pitx3. We propose a role for this feedback circuit in the fine-tuning of dopaminergic behaviors such as locomotion.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
miR-133b is enriched in midbrain dopaminergic neurons and was found to be deficient in the parkinsonian midbrain.
“miR-133b is enriched in midbrain dopaminergic neurons and was found to be deficient in the parkinsonian midbrain [101].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [101]
miR-27a/b are expressed in SN of human midbrain.
“miR-27a/b are expressed in SN of human midbrain (Additional file 2a) [34–36]”
From miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1) (2016) · cites this paper as [35]
The expression-analysis passage (p. 2) describes human midbrain samples and a panel of miRNAs, but identifies miR-133b rather than miR-27a/b. Searches for miR-27a/b and substantia nigra expression found no passage in our copy establishing the claimed expression. (LLM, conf=0.75)
Experimental — accuracy not yet measuredmiR-27a/b are expressed in human midbrain.
“Several previous studies showed that miR-27a/b are expressed in human midbrain [34–36].”
From miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1) (2016) · cites this paper as [35]
The expression-analysis passage (p. 2) describes a panel of approximately 230 miRNAs tested in human midbrain, but does not identify miR-27a or miR-27b. Searches for “miR-27a miR-27b human midbrain” and “miR-27” found no passage in our copy establishing their expression there. (LLM, conf=0.73)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A microRNA array reveals extensive regulation of microRNAs during brain development
KRICHEVSKY, A. M., KING, K. S., DONAHUE, C. P., KHRAPKO, K., & KOSIK, K. S. (2003) · RNA · doi:10.1261/rna.5980303 · Cited by 1,040 · see citing works
Identification of intrinsic determinants of midbrain dopamine neurons
Andersson, E., Tryggvason, U., Deng, Q., Friling, S., Alekseenko, Z., Robert, B., Perlmann, T., & Ericson, J. (2006) · Cell · doi:10.1016/j.cell.2005.10.037 · Cited by 587 · see citing works
FACS-array profiling of striatal projection neuron subtypes in juvenile and adult mouse brains
Lobo, M. K., Karsten, S. L., Gray, M., Geschwind, D. H., & Yang, X. W. (2006) · Nature Neuroscience · doi:10.1038/nn1654 · Cited by 411 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The widespread regulation of microRNA biogenesis, function and decay
Krol, J., Loedige, I., & Filipowicz, W. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2843 · Cited by 4,672 · see citing works
Translational control of long-lasting synaptic plasticity and memory
Costa-Mattioli, M., Sossin, W. S., Klann, E., & Sonenberg, N. (2009) · Neuron · doi:10.1016/j.neuron.2008.10.055 · Cited by 944 · see citing works
Cogswell, J. P., Ward, J., Taylor, I. A., Waters, M., Shi, Y., Cannon, B., Kelnar, K., Kemppainen, J., Brown, D., Chen, C., et al. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14103 · Cited by 943 · see citing works
Packer, A. N., Xing, Y., Harper, S. Q., Jones, L., & Davidson, B. L. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2390-08.2008 · Cited by 679 · see citing works
Repression of α-synuclein expression and toxicity by microRNA-7
Junn, E., Lee, K.-W., Jeong, B. S., Chan, T. W., Im, J.-Y., & Mouradian, M. M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0906277106 · Cited by 634 · see citing works
Alterations of the microRNA network cause neurodegenerative disease
Hébert, S. S., & De Strooper, B. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2008.12.003 · Cited by 452 · see citing works
MicroRNA regulation of Alzheimer's Amyloid precursor protein expression
Hébert, S. S., Horré, K., Nicolaï, L., Bergmans, B., Papadopoulou, A. S., Delacourte, A., & De Strooper, B. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.11.009 · Cited by 436 · see citing works
De Pietri Tonelli, D., Pulvers, J. N., Haffner, C., Murchison, E. P., Hannon, G. J., & Huttner, W. B. (2008) · Development · doi:10.1242/dev.025080 · Cited by 343 · see citing works
Self-citationSmalheiser, N. R., Lugli, G., Rizavi, H. S., Torvik, V. I., Turecki, G., & Dwivedi, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033201 · Cited by 324 · see citing works
Sun, G., Li, G., Li, D., Huang, W., Zhang, R., Zhang, H., Duan, Y., & Wang, B. (2018) · Materials Science and Engineering C · doi:10.1016/j.msec.2018.04.006 · Cited by 314 · see citing works
Wang, X., Liu, P., Zhu, H., Xu, Y., Ma, C., Dai, X., Huang, L., Liu, Y., Zhang, L., & Qin, C. (2009) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2009.08.006 · Cited by 271 · see citing works
microRNA as Repressors of Stress-Induced Anxiety: The Case of Amygdalar miR-34
Haramati, S., Navon, I., Issler, O., Ezra-Nevo, G., Gil, S., Zwang, R., Hornstein, E., & Chen, A. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.1673-11.2011 · Cited by 252 · see citing works
Cho, H., Proll, S. C., Szretter, K. J., Katze, M. G., Gale, M., & Diamond, M. S. (2013) · Nature Medicine · doi:10.1038/nm.3108 · Cited by 228 · see citing works
An updated role of microRNA-124 in central nervous system disorders: a review
Sun, Y., Luo, Z.-M., Guo, X.-M., Su, D.-F., & Liu, X. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00193 · Cited by 223 · see citing works
Parkinson’s disease as a result of aging
Rodriguez, M., Rodriguez‐Sabate, C., Morales, I., Sanchez, A., & Sabate, M. (2015) · Aging Cell · doi:10.1111/acel.12312 · Cited by 214 · see citing works
An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model
Selvamani, A., Sathyan, P., Miranda, R. C., & Sohrabji, F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032662 · Cited by 217 · see citing works
Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain
Boudreau, R. L., Jiang, P., Gilmore, B. L., Spengler, R. M., Tirabassi, R., Nelson, J. A., Ross, C. A., Xing, Y., & Davidson, B. L. (2014) · Neuron · doi:10.1016/j.neuron.2013.10.062 · Cited by 217 · see citing works
General Principals of miRNA Biogenesis and Regulation in the Brain
O'Carroll, D., & Schaefer, A. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.87 · Cited by 205 · see citing works
MicroRNAs and neurodegeneration: role and impact
Abe, M., & Bonini, N. M. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.08.013 · Cited by 190 · see citing works
Kim, J., Fiesel, F. C., Belmonte, K. C., Hudec, R., Wang, W.-X., Kim, C., Nelson, P. T., Springer, W., & Kim, J. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0121-4 · Cited by 163 · see citing works
Self-citationHsieh, J., & Eisch, A. J. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.01.008 · Cited by 144 · see citing works
Illumination controls differentiation of dopamine neurons regulating behaviour
Dulcis, D., & Spitzer, N. C. (2008) · Nature · doi:10.1038/nature07569 · Cited by 115 · see citing works
Briggs, C. E., Wang, Y., Kong, B., Woo, T.-U. W., Iyer, L. K., & Sonntag, K. C. (2015) · Brain Research · doi:10.1016/j.brainres.2015.05.021 · Cited by 113 · see citing works
RhoA Signaling in Neurodegenerative Diseases
Schmidt, S. I., Blaabjerg, M., Freude, K., & Meyer, M. (2022) · Cells · doi:10.3390/cells11091520 · Cited by 110 · see citing works
MiRNA Profile in the Substantia Nigra of Parkinson’s Disease and Healthy Subjects
Cardo, L. F., Coto, E., Ribacoba, R., Menéndez, M., Moris, G., Suárez, E., & Alvarez, V. (2014) · Journal of Molecular Neuroscience · doi:10.1007/s12031-014-0428-y · Cited by 75 · see citing works
Potential Treatment of Parkinson’s Disease with Omega-3 Polyunsaturated Fatty Acids
Li, P., & Song, C. (2022) · Nutritional Neuroscience · doi:10.1080/1028415x.2020.1735143 · Cited by 74 · see citing works
Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156-controlled gene network
Wei, S., Gruber, M. Y., Yu, B., Gao, M.-J., Khachatourians, G. G., Hegedus, D. D., Parkin, I. A., & Hannoufa, A. (2012) · BMC Plant Biology · doi:10.1186/1471-2229-12-169 · Cited by 73 · see citing works
Su, C., Yang, X., & Lou, J. (2016) · Brain Research · doi:10.1016/j.brainres.2016.05.011 · Cited by 73 · see citing works
Gstir, R., Schafferer, S., Scheideler, M., Misslinger, M., Griehl, M., Daschil, N., Humpel, C., Obermair, G. J., Schmuckermair, C., Striessnig, J., et al. (2014) · RNA · doi:10.1261/rna.047225.114 · Cited by 36 · see citing works
Murphy, R., Villegas-Salmerón, J., Sanz-Rodriguez, A., Engel, T., Mooney, C., Henshall, D. C., & Jimenez-Mateos, E. M. (2025) · PLOS One · doi:10.1371/journal.pone.0326401 · Cited by 3 · see citing works
- Authors
- Kim, J., Inoue, K., Ishii, J., Vanti, W. B., Voronov, S. V., Murchison, E., Hannon, G., & Abeliovich, A.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Abeliovich, Asa
- Venue
- Science
- Published
- 2007-08-31
- Volume
- 317
- Issue
- 5842
- Pages
- 1220-1224
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2782470
- OpenAlex
- W2019028138
- Cited by
- 1,187
- References
- 3
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 30 · 2023: 30 · 2022: 54 · 2021: 53 · 2020: 49 · 2019: 61 · 2018: 52 · 2017: 65 · 2016: 64 · 2015: 75 · 2014: 81 · 2013: 107 · 2012: 94
- FWCI
- 29.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS064433)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- microRNA, miR-133b, midbrain dopaminergic neurons, Parkinson's disease, Pitx3, negative feedback circuit, transcriptional regulation, locomotion
- MeSH terms
- Aged, Aged, 80 and over, Animals, Cell Differentiation, Cell Line, Cells, Cultured, Dopamine, Female, Gene Expression Regulation, Humans, Locomotion, Male, Mesencephalon, Middle Aged, Models, Biological, Neurons, Parkinson Disease, Transcription Factors, Transcription, Genetic, Homeodomain Proteins, 3' Untranslated Regions, Feedback, Physiological, MicroRNAs, Ribonuclease III, Mice, Rats, Embryonic Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
