CoChat
Sign Up
Cited by 426

Cerebellar neurodegeneration in the absence of microRNAs

Schaefer, Anne, O'Carroll, Dónal, Tan, Chan Lek, Hillman, Dean, Sugimori, Mutsuyuki, Llinas, Rodolfo, Greengard, Paul·2007·The Journal of Experimental Medicine
DOI 10.1084/jem.20070823PMC PMC2118654
Open this paper in CoChat — free account

Abstract

Genome-encoded microRNAs (miRNAs) are potent regulators of gene expression. The significance of miRNAs in various biological processes has been suggested by studies showing an important role of these small RNAs in regulation of cell differentiation. However, the role of miRNAs in regulation of differentiated cell physiology is not well established. Mature neurons express a large number of distinct miRNAs, but the role of miRNAs in postmitotic neurons has not been examined. Here, we provide evidence for an essential role of miRNAs in survival of differentiated neurons. We show that conditional Purkinje cell–specific ablation of the key miRNA-generating enzyme Dicer leads to Purkinje cell death. Deficiency in Dicer is associated with progressive loss of miRNAs, followed by cerebellar degeneration and development of ataxia. The progressive neurodegeneration in the absence of Dicer raises the possibility of an involvement of miRNAs in neurodegenerative disorders.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1084/jem.20070823

Cites

4 of 4 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Conditional ablation of Dicer in murine post-mitotic Purkinje cells results in progressive loss of miRNAs, cerebellar degeneration, and development of ataxia.

    “In addition, conditional ablation of Dicer in murine post-mitotic Purkinje cells resulted in progressive loss of miRNAs, cerebellar degeneration, and development of ataxia (Schaefer et al. 2007).”

    From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Schaefer et al. 2007

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

Flagged first, then by citations

Research works printed but not linked: 26

  1. [1]Ambros, V. 2004. The functions of animal microRNAs. Nature. 431: 350–355. 15372042
  2. [2]Bartel, D.P. 2004. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116: 281–297. 14744438
  3. [3]He, L., and G.J. Hannon. 2004. MicroRNAs: small RNAs with a big role in gene regulation. Nat. Rev. Genet. 5: 522–531. 15211354
  4. [4]Cobb, B.S., T.B. Nesterova, E. Thompson, A. Hertweck, E. O'Connor, J. Godwin, C.B. Wilson, N. Brockdorff, A.G. Fisher, S.T. Smale, and M. Merkenschlager. 2005. T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J. Exp. Med. 201: 1367–1373. 15867090 PMC2213187
  5. [5]Cobb, B.S., A. Hertweck, J. Smith, E. O'Connor, D. Graf, T. Cook, S.T. Smale, S. Sakaguchi, F.J. Livesey, A.G. Fisher, and M. Merkenschlager. 2006. A role for Dicer in immune regulation. J. Exp. Med. 203: 2519–2527. 17060477 PMC2118134
  6. [6]Muljo, S.A., K.M. Ansel, C. Kanellopoulou, D.M. Livingston, A. Rao, and K. Rajewsky. 2005. Aberrant T cell differentiation in the absence of Dicer. J. Exp. Med. 202: 261–269. 16009718 PMC2212998
  7. [8]Harfe, B.D., M.T. McManus, J.H. Mansfield, E. Hornstein, and C.J. Tabin. 2005. The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc. Natl. Acad. Sci. USA. 102: 10898–10903. 16040801 PMC1182454
  8. [9]Li, Q.J., J. Chau, P.J. Ebert, G. Sylvester, H. Min, G. Liu, R. Braich, M. Manoharan, J. Soutschek, P. Skare, et al. 2007. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell. 129: 147–161. 17382377
  9. [10]Zhao, Y., J.F. Ransom, A. Li, V. Vedantham, M. von Drehle, A.N. Muth, T. Tsuchihashi, M.T. McManus, R.J. Schwartz, and D. Srivastava. 2007. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell. 129: 303–317. 17397913
  10. [11]van Rooij, E., L.B. Sutherland, X. Qi, J.A. Richardson, J. Hill, and E.N. Olson. 2007. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science. 316: 575–579. 17379774
  11. [12]Babak, T., W. Zhang, Q. Morris, B.J. Blencowe, and T.R. Hughes. 2004. Probing microRNAs with microarrays: tissue specificity and functional inference. RNA. 10: 1813–1819. 15496526 PMC1370668
  12. [13]Barad, O., E. Meiri, A. Avniel, R. Aharonov, A. Barzilai, I. Bentwich, U. Einav, S. Gilad, P. Hurban, Y. Karov, et al. 2004. MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues. Genome Res. 14: 2486–2494. 15574827 PMC534673
  13. [14]Miska, E.A., E. Alvarez-Saavedra, M. Townsend, A. Yoshii, N. Sestan, P. Rakic, M. Constantine-Paton, and H.R. Horvitz. 2004. Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol. 5: R68. 15345052 PMC522875
  14. [16]Lagos-Quintana, M., R. Rauhut, A. Yalcin, J. Meyer, W. Lendeckel, and T. Tuschl. 2002. Identification of tissue-specific microRNAs from mouse. Curr. Biol. 12: 735–739. 12007417
  15. [19]Lim, L.P., N.C. Lau, P. Garrett-Engele, A. Grimson, J.M. Schelter, J. Castle, D.P. Bartel, P.S. Linsley, and J.M. Johnson. 2005. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 433: 769–773. 15685193
  16. [20]Vo, N., M.E. Klein, O. Varlamova, D.M. Keller, T. Yamamoto, R.H. Goodman, and S. Impey. 2005. A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc. Natl. Acad. Sci. USA. 102: 16426–16431. 16260724 PMC1283476
  17. [21]Schratt, G.M., F. Tuebing, E.A. Nigh, C.G. Kane, M.E. Sabatini, M. Kiebler, and M.E. Greenberg. 2006. A brain-specific microRNA regulates dendritic spine development. Nature. 439: 283–289. 16421561
  18. [22]Bernstein, E., A.A. Caudy, S.M. Hammond, and G.J. Hannon. 2001. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 409: 363–366. 11201747
  19. [23]Bernstein, E., S.Y. Kim, M.A. Carmell, E.P. Murchison, H. Alcorn, M.Z. Li, A.A. Mills, S.J. Elledge, K.V. Anderson, and G.J. Hannon. 2003. Dicer is essential for mouse development. Nat. Genet. 35: 215–217. 14528307
  20. [24]Zhang, X.M., A.H. Ng, J.A. Tanner, W.T. Wu, N.G. Copeland, N.A. Jenkins, and J.D. Huang. 2004. Highly restricted expression of Cre recombinase in cerebellar Purkinje cells. Genesis. 40: 45–51. 15354293
  21. [25]Mao, X., Y. Fujiwara, A. Chapdelaine, H. Yang, and S.H. Orkin. 2001. Activation of EGFP expression by Cre-mediated excision in a new ROSA26 reporter mouse strain. Blood. 97: 324–326. 11133778
  22. [26]Wetts, R., and K. Herrup. 1983. Direct correlation between Purkinje and granule cell number in the cerebella of lurcher chimeras and wild-type mice. Brain Res. 312: 41–47. 6652508
  23. [27]Caddy, K.W., and T.J. Biscoe. 1979. Structural and quantitative studies on the normal C3H and Lurcher mutant mouse. Philos. Trans. R. Soc. Lond. B Biol. Sci. 287: 167–201. 41272
  24. [28]Lee, K.W., Y. Kim, A.M. Kim, K. Helmin, A.C. Nairn, and P. Greengard. 2006. Cocaine-induced dendritic spine formation in D1 and D2 dopamine receptor-containing medium spiny neurons in nucleus accumbens. Proc. Natl. Acad. Sci. USA. 103: 3399–3404. 16492766 PMC1413917
  25. [29]Kloosterman, W.P., E. Wienholds, E. de Bruijn, S. Kauppinen, and R.H. Plasterk. 2006. In situ detection of miRNAs in animal embryos using LNA-modified oligonucleotide probes. Nat. Methods. 3: 27–29. 16369549
  26. [30]Hirata, K., M. Nakagawa, F.J. Urbano, M.D. Rosato-Siri, J.E. Moreira, O.D. Uchitel, M. Sugimori, and R. Llinas. 1999. Reduced facilitation and vesicular uptake in crustacean and mammalian neuromuscular junction by T-588, a neuroprotective compound. Proc. Natl. Acad. Sci. USA. 96: 14588–14593. 10588749 PMC24480

Cited by

Sorted by citations

Authors
Schaefer, A., O'Carroll, D., Tan, C. L., Hillman, D., Sugimori, M., Llinas, R., & Greengard, P.
Affiliations
  • 1Laboratory of Molecular and Cellular Neuroscience and
  • 2Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, NY 10021
  • 3Department of Otolaryngology and
  • 4Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2007-07-02
Volume
204
Issue
7
Pages
1553-1558
ISSN
  • 1540-9538
  • 0022-1007
DOI
10.1084/jem.20070823
PMC
PMC2118654
Cited by
426
References
4
Language
en

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