Universität zu Köln

Kye, Min Jeong ORCID: 0000-0002-1323-7256, Niederst, Emily D., Wertz, Mary H., Goncalves, Ines do Carmo G., Akten, Bikem, Dover, Katarzyna Z., Peters, Miriam, Riessland, Markus ORCID: 0000-0003-2592-5045, Neveu, Pierre ORCID: 0000-0003-4939-3418, Wirth, Brunhilde ORCID: 0000-0003-4051-5191, Kosik, Kenneth S., Sardi, S. Pablo, Monani, Umrao R., Passini, Marco A. and Sahin, Mustafa (2014). SMN regulates axonal local translation via miR-183/mTOR pathway. Hum. Mol. Genet., 23 (23). S. 6318 - 6332. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2083

Full text not available from this repository.

Abstract

Reduced expression of SMN protein causes spinal muscular atrophy (SMA), a neurodegenerative disorder leading to motor neuron dysfunction and loss. However, the molecular mechanisms by which SMN regulates neuronal dysfunction are not fully understood. Here, we report that reduced SMN protein level alters miRNA expression and distribution in neurons. In particular, miR-183 levels are increased in neurites of SMN-deficient neurons. We demonstrate that miR-183 regulates translation of mTor via direct binding to its 3' UTR. Interestingly, local axonal translation of mTor is reduced in SMN-deficient neurons, and this can be recovered by miR-183 inhibition. Finally, inhibition of miR-183 expression in the spinal cord of an SMA mouse model prolongs survival and improves motor function of Smn-mutant mice. Together, these observations suggest that axonal miRNAs and the mTOR pathway are previously unidentified molecular mechanisms contributing to SMA pathology.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kye, Min Jeong UNSPECIFIED orcid.org/0000-0002-1323-7256 UNSPECIFIED Niederst, Emily D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wertz, Mary H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Goncalves, Ines do Carmo G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Akten, Bikem UNSPECIFIED UNSPECIFIED UNSPECIFIED Dover, Katarzyna Z. UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Miriam UNSPECIFIED UNSPECIFIED UNSPECIFIED Riessland, Markus UNSPECIFIED orcid.org/0000-0003-2592-5045 UNSPECIFIED Neveu, Pierre UNSPECIFIED orcid.org/0000-0003-4939-3418 UNSPECIFIED Wirth, Brunhilde UNSPECIFIED orcid.org/0000-0003-4051-5191 UNSPECIFIED Kosik, Kenneth S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sardi, S. Pablo UNSPECIFIED UNSPECIFIED UNSPECIFIED Monani, Umrao R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Passini, Marco A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sahin, Mustafa UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-422500
DOI:	10.1093/hmg/ddu350
Journal or Publication Title:	Hum. Mol. Genet.
Volume:	23
Number:	23
Page Range:	S. 6318 - 6332
Date:	2014
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2083
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SPINAL MUSCULAR-ATROPHY; MOTOR-NEURON PROTEIN; MESSENGER-RNA; GENE-PRODUCT; SYMPATHETIC NEURONS; CORTICAL-NEURONS; GROWTH CONES; SURVIVAL; COMPLEX; DISEASE Multiple languages Biochemistry & Molecular Biology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42250