Cytoplasmic cleavage of IMPA1 3' UTR is necessary for maintaining axon integrity.
Ontology highlight
ABSTRACT:
SUBMITTER: Andreassi C
PROVIDER: S-EPMC7918530 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The 3’ untranslated regions (3’UTRs) of messenger RNAs (mRNA) are non-coding sequences involved in many aspects of mRNA metabolism, including intracellular localisation and translation. Incorrect processing and delivery of mRNA causes severe developmental defects and has been implicated in many neurological disorders. Here, we use deep sequencing to show that in sympathetic neuron axons, the 3’UTRs of many transcripts undergo cleavage, generating isoforms that express the coding sequence with a short 3’UTR, and stable 3’UTR-derived fragments of unknown function. Cleavage of the long 3’UTR of Inositol Monophosphatase 1 ( IMPA1 ), mediated by a protein complex containing the endonuclease Ago2 and the RNA binding protein HuD, generates a translatable isoform that is necessary for maintaining the integrity of sympathetic neuron axons. Thus, our study provides a new mechanism of mRNA metabolism that simultaneously regulates local protein synthesis and generates a yet undescribed class of non-coding RNAs.
2020-12-31 | GSE160025 | GEO
Project description:Cytoplasmic cleavage of IMPA1 3’UTR is necessary for maintaining axon integrity.
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Project description:BACKGROUND: Bamboo mosaic virus (BaMV) and the Potato virus X (PVX) are members of the genus Potexvirus and have a single-stranded positive-sense RNA genome. The 3'-untranslated region (UTR) of the BaMV RNA genome was mapped structurally into ABC (a cloverleaf-like), D (a stem-loop), and E (pseudoknot) domains. The BaMV replicase complex that was isolated from the infected plants was able to recognize the 3' UTR of PVX RNA to initiate minus-strand RNA synthesis in vitro. RESULTS: To investigate whether the 3' UTR of PVX RNA is also compatible with BaMV replicase in vivo, we constructed chimera mutants using a BaMV backbone containing the PVX 3' UTR, which was inserted in or used to replace the various domains in the 3' UTR of BaMV. None of the mutants, except for the mutant with the PVX 3' UTR inserted upstream of the BaMV 3' UTR, exhibited a detectable accumulation of viral RNA in Nicotiana benthamiana plants. The in vitro BaMV RdRp replication assay demonstrated that the RNA products were generated by the short RNA transcripts, which were derived from the chimera mutants to various extents. Furthermore, the Vmax/KM of the BaMV 3' UTR (rABCDE) was approximately three fold higher than rABCP, rP, and rDE in minus-strand RNA synthesis. These mutants failed to accumulate viral products in protoplasts and plants, but were adequately replicated in vitro. CONCLUSIONS: Among the various studied BaMV/PVX chimera mutants, the BaMV-S/PABCDE that contained non-interrupted BaMV 3' UTR was the only mutant that exhibited a wild-type level of viral product accumulation in protoplasts and plants. These results indicate that the continuity of the domains in the 3' UTR of BaMV RNA was not interrupted and the domains were not replaced with the 3' UTR of PVX RNA in vivo.
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