Huo, Qing; Kayikci, Melis; Odermatt, Philipp; Meyer, Kathrin; Michels, Olivia; Saxena, Smita; Ule, Jernej; Schümperli, Daniel (2014). Splicing changes in SMA mouse motoneurons and SMN-depleted neuroblastoma cells: evidence for involvement of splicing regulatory proteins. RNA biology, 11(11), pp. 1430-1446. Landes Bioscience 10.1080/15476286.2014.996494
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Spinal Muscular Atrophy (SMA) is caused by deletions or mutations in the Survival Motor Neuron 1 (SMN1) gene. The second gene copy, SMN2, produces some, but not enough, functional SMN protein. SMN is essential to assemble small nuclear ribonucleoproteins (snRNPs) that form the spliceosome. However, it is not clear whether SMA is caused by defects in this function that could lead to splicing changes in all tissues, or by the impairment of an additional, less well characterized, but motoneuron-specific SMN function. We addressed the first possibility by exon junction microarray analysis of motoneurons (MNs) isolated by laser capture microdissection from a severe SMA mouse model. This revealed changes in multiple U2-dependent splicing events. Moreover, splicing appeared to be more strongly affected in MNs than in other cells. By testing mutiple genes in a model of progressive SMN depletion in NB2a neuroblastoma cells, we obtained evidence that U2-dependent splicing changes occur earlier than U12-dependent ones. As several of these changes affect genes coding for splicing regulators, this may acerbate the splicing response induced by low SMN levels and induce secondary waves of splicing alterations.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
08 Faculty of Science > Department of Biology > Institute of Cell Biology 08 Faculty of Science > Department of Biology > Institute of Cell Biology > RNA |
UniBE Contributor: |
Huo, Qing, Odermatt, Philipp, Saxena, Smita, Schümperli, Daniel |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science |
ISSN: |
1547-6286 |
Publisher: |
Landes Bioscience |
Language: |
English |
Submitter: |
Prof. Smita Saxena |
Date Deposited: |
08 May 2015 08:28 |
Last Modified: |
05 Dec 2022 14:46 |
Publisher DOI: |
10.1080/15476286.2014.996494 |
PubMed ID: |
25692239 |
Uncontrolled Keywords: |
ESE, exonic splicing enhancer FCS, fetal calf serum MN, motoneuron NMD, nonsense-mediated mRNA decay NMJ, neuromuscular junction, PCR RT, reverse transcription SMA, Spinal Muscular Atrophy SMN, Survival Motor Neuron Spinal Muscular Atrophy TcRβ, T-cell receptor β chain exon junction microarray hz, heterozygote, LCM laser capture microdissection major spliceosome minor spliceosome motoneurons neurodegerative disease polymerase chain reaction, qPCR real-time (quantitative) PCR sh, short hairpin snRNA, small nuclear ribonucleic acid snRNP assembly snRNP, small nuclear ribonucleoprotein splicing splicing regulators |
BORIS DOI: |
10.7892/boris.68130 |
URI: |
https://boris.unibe.ch/id/eprint/68130 |
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