RNA binding protein AUF1/HNRNPD regulates nuclear export, stability and translation of SNCA transcripts
Alpha-synuclein (SNCA) accumulation plays a central role in the pathogenesis of Parkinson's disease. Determining and interfering with the mechanisms that control SNCA expression is one approach to limiting disease progression. Currently, most of our understanding of SNCA regulation is protein-b...
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Veröffentlicht in: | Open biology 2023-11, Vol.13 (11), p.230158-230158 |
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Sprache: | eng |
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Zusammenfassung: | Alpha-synuclein (SNCA) accumulation plays a central role in the pathogenesis of Parkinson's disease. Determining and interfering with the mechanisms that control SNCA expression is one approach to limiting disease progression. Currently, most of our understanding of SNCA regulation is protein-based. Post-transcriptional mechanisms directly regulating
SNCA
mRNA expression via its 3′ untranslated region (3′UTR) were investigated here. Mass spectrometry of proteins pulled down from murine brain lysates using a biotinylated
SNCA
3′UTR revealed multiple RNA-binding proteins, of which HNRNPD/AUF1 was chosen for further analysis. AUF1 bound both proximal and distal regions of the
SNCA
3′UTR, but not the 5′UTR or CDS. In the nucleus, AUF1 attenuated
SNCA
pre-mRNA maturation and was indispensable for the export of
SNCA
transcripts. AUF1 destabilized
SNCA
transcripts in the cytosol, primarily those with shorter 3′UTRs, independently of microRNAs by recruiting the CNOT1-CNOT7 deadenylase complex to trim the polyA tail. Furthermore, AUF1 inhibited
SNCA
mRNA binding to ribosomes. These data identify AUF1 as a multi-tasking protein regulating maturation, nucleocytoplasmic shuttling, stability and translation of
SNCA
transcripts. |
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ISSN: | 2046-2441 2046-2441 |
DOI: | 10.1098/rsob.230158 |