PUBLICATION
Cytoplasmic pool of U1 spliceosome protein SNRNP70 shapes the axonal transcriptome and regulates motor connectivity
- Authors
- Nikolaou, N., Gordon, P.M., Hamid, F., Taylor, R., Lloyd-Jones, J., Makeyev, E.V., Houart, C.
- ID
- ZDB-PUB-221118-5
- Date
- 2022
- Source
- Current biology : CB 32(23): 5099-5115.e8 (Journal)
- Registered Authors
- Houart, Corinne, Nikolaou, Nikolas
- Keywords
- Z+agrn, alternative splicing, mRNA processing, mRNA stability, mRNA transport, motor neurons, neurodegenerative diseases, neuromuscular junction, ribonucleoprotein complexes, synaptic connectivity
- MeSH Terms
-
- Animals
- RNA Precursors*
- Zebrafish*/genetics
- PubMed
- 36384140 Full text @ Curr. Biol.
Citation
Nikolaou, N., Gordon, P.M., Hamid, F., Taylor, R., Lloyd-Jones, J., Makeyev, E.V., Houart, C. (2022) Cytoplasmic pool of U1 spliceosome protein SNRNP70 shapes the axonal transcriptome and regulates motor connectivity. Current biology : CB. 32(23):5099-5115.e8.
Abstract
Regulation of pre-mRNA splicing and polyadenylation plays a profound role in neurons by diversifying the proteome and modulating gene expression in response to physiological cues. Although most of the pre-mRNA processing is thought to occur in the nucleus, numerous splicing regulators are also found in neurites. Here, we show that U1-70K/SNRNP70, a component of the major spliceosome, localizes in RNA-associated granules in zebrafish axons. We identify the extra-nuclear SNRNP70 as an important regulator of motor axonal growth, nerve-dependent acetylcholine receptor (AChR) clustering, and neuromuscular synaptogenesis. This cytoplasmic pool has a protective role for a limited number of transcripts regulating their abundance and trafficking inside axons. Moreover, non-nuclear SNRNP70 regulates splice variants of transcripts such as agrin, thereby controlling synapse formation. Our results point to an unexpected, yet essential, function of non-nuclear SNRNP70 in axonal development, indicating a role of spliceosome proteins in cytoplasmic RNA metabolism during neuronal connectivity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping