Proteomics

Dataset Information

0

SRRM4/nSR100 directs neuronal-specific microexon splicing of TAF1 mRNA involved in X-linked Dystonia-Parkinsonism


ABSTRACT: X-linked dystonia-parkinsonism is a neurodegenerative disease, which is caused by a SVA retrotransposon insertion within TAF1, gene encoding an integral component of the basal transcription factor TFIID. The SVA insertion has been shown to induce defects both in biosynthesis and in alternative splicing of TAF1 mRNA in various cell types. This includes the reduction of a neuron-specific isoform of TAF1 mRNA generated by inclusion of the evolutionary conserved microexon 34’ (TAF1-34’). In this study, we investigated the tissue distribution of TAF1-34’ mRNA and protein and the neuron-specific mechanism sustaining its alternative splicing. Using isoform-specific RNA probes and antibodies, we observe that canonical TAF1 and TAF1-34’ have different distributions in the brain. To our knowledge, this is the first in situ detection of a microexon. We find that the differential expression of these two isoforms distinguishes proliferating from post-mitotic neurons in vitro and in vivo. Knockdown and ectopic expression experiments in cell lines demonstrated that the neuron-specific splicing factor nSR100/SRRM4 is directing the inclusion of microexon 34’ into TAF1 mRNA. These results show that SRRM4 regulates temporal and spatial distribution of alternative TAF1 mRNAs to generate a neuron-specific isoform of basal transcription factor TFIID.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Oliver Schilling  

LAB HEAD: Oliver Schilling

PROVIDER: PXD009905 | Pride | 2020-05-26

REPOSITORIES: Pride

altmetric image

Publications


Neuronal microexons represent the most highly conserved class of alternative splicing events and their timed expression shapes neuronal biology, including neuronal commitment and differentiation. The six-nt microexon 34' is included in the neuronal form of <i>TAF1</i> mRNA, which encodes the largest subunit of the basal transcription factor TFIID. In this study, we investigate the tissue distribution of <i>TAF1-34'</i> mRNA and protein and the mechanism responsible for its neuronal-specific spli  ...[more]

Similar Datasets

| E-GEOD-45873 | biostudies-arrayexpress
2006-01-10 | GSE3006 | GEO
2023-07-04 | PXD036358 | Pride
2022-03-02 | PXD011211 | Pride
2023-11-01 | GSE245093 | GEO
2006-03-20 | GSE3346 | GEO
2006-03-20 | GSE3345 | GEO
2013-05-01 | GSE45873 | GEO
2017-08-02 | GSE97081 | GEO
| phs001525 | dbGaP